| 1. |
- Abedini, Sadollah, et al.
(författare)
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Cerebrovascular events in renal transplant recipients
- 2009
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 87:1, s. 112-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The incidence of stroke and risk factors for different subtypes of cerebrovascular (CBV) events in renal transplant recipients have not been examined in any large prospective controlled trial. METHODS: The Assessment of Lescol in Renal Transplantation was a randomized, double-blind, placebo-controlled study of the effect of fluvastatin (40-80 mg) daily on cardiovascular, and renal outcomes in renal transplant recipients. Patients initially randomized to fluvastatin or placebo in the 5 to 6 year trial was offered open-label fluvastatin in a 2-year extension to the original study. We investigated the incidence of stroke and risk factors for ischemic and hemorrhagic CBV events in 2102 renal graft recipients participating in the Assessment of Lescol in Renal Transplantation core and extension trial with a mean follow-up of 6.7 years. RESULTS: The incidence and type of CBV events did not differ between the lipid lowering arm and the placebo arm. A total of 184 (8.8%, 95% confidence interval 4.6-12.9) of 2102 patients experienced a CBV event during follow-up, corresponding to an incidence of 1.3% CBV event per year. The mortality for patients experiencing a hemorrhagic stroke was 48% (13 of 27), whereas the mortality for ischemic strokes was 6.0% (8 of 133). Diabetes mellitus, previous CBV event, age, and serum creatinine were independent risk factors for cerebral ischemic events. The risk of a hemorrhagic cerebral event was increased by diabetes mellitus, polycystic kidney disease, left ventricular hypertrophy, and systolic blood pressure. INTERPRETATION: Risk factors for CBV events in renal transplant recipients differ according to subtype.
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| 2. |
- Baigent, Colin, et al.
(författare)
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The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection) : a randomised placebo-controlled trial
- 2011
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 377:9784, s. 2181-2192
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Tidskriftsartikel (refereegranskat)abstract
- Background Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infarction, ischaemic stroke, and the need for coronary revascularisation in people without kidney disease, but its effects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial aimed to assess the efficacy and safety of the combination of simvastatin plus ezetimibe in such patients. Methods This randomised double-blind trial included 9270 patients with chronic kidney disease (3023 on dialysis and 6247 not) with no known history of myocardial infarction or coronary revascularisation. Patients were randomly assigned to simvastatin 20 mg plus ezetimibe 10 mg daily versus matching placebo. The key prespecified outcome was first major atherosclerotic event (non-fatal myocardial infarction or coronary death, non-haemorrhagic stroke, or any arterial revascularisation procedure). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00125593, and I SRCTN54137607. Findings 4650 patients were assigned to receive simvastatin plus ezetimibe and 4620 to placebo. Allocation to simvastatin plus ezetimibe yielded an average LDL cholesterol difference of 0.85 mmol/L (SE 0.02; with about two-thirds compliance) during a median follow-up of 4.9 years and produced a 17% proportional reduction in major atherosclerotic events (526 [11.3%] simvastatin plus ezetimibe vs 619 [13.4%] placebo; rate ratio [RR] 0.83, 95% CI 0.74-0.94; log-rank p=0.0021). Non-significantly fewer patients allocated to simvastatin plus ezetimibe had a non-fatal myocardial infarction or died from coronary heart disease (213 [4.6%] vs 230 [5.0%]; RR 0.92,95% CI 0.76-1.11; p=0.37) and there were significant reductions in non-haemorrhagic stroke (131 [2.8%] vs 174 [3.8%]; RR 0.75,95% CI 0.60-0.94; p=0.01) and arterial revascularisation procedures (284 [6.1%] vs 352 [7.6%]; RR 0.79, 95% CI 0.68-0.93; p=0.0036). After weighting for subgroup-specific reductions in LDL cholesterol, there was no good evidence that the proportional effects on major atherosclerotic events differed from the summary rate ratio in any subgroup examined, and, in particular, they were similar in patients on dialysis and those who were not. The excess risk of myopathy was only two per 10 000 patients per year of treatment with this combination (9 [0.2%] vs 5 [0.1%]). There was no evidence of excess risks of hepatitis (21 [0.5%] vs 18 [0.4%]), gallstones (106 [2.3%] vs 106 [2.3%]), or cancer (438 [9.4%] vs 439 [9.5%], p=0.89) and there was no significant excess of death from any non-vascular cause (668 [14.4%] vs 612 [13.2%], p=0.13). Interpretation Reduction of LDL cholesterol with simvastatin 20 mg plus ezetimibe 10 mg daily safely reduced the incidence of major atherosclerotic events in a wide range of patients with advanced chronic kidney disease.
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| 3. |
- Bredewold, Obbo W, et al.
(författare)
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Cardiovascular Risk Following Conversion to Belatacept From a Calcineurin Inhibitor in Kidney Transplant Recipients : A Randomized Clinical Trial
- 2023
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Ingår i: Kidney Medicine. - : Elsevier. - 2590-0595. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE & OBJECTIVE: In kidney transplant recipients (KTRs), a belatacept-based immunosuppressive regimen is associated with beneficial effects on cardiovascular (CV) risk factors compared with calcineurin inhibitor (CNI)-based regimens. Our objective was to compare the calculated CV risk between belatacept and CNI (predominantly tacrolimus) treatments using a validated model developed for KTRs.STUDY DESIGN: Prospective, randomized, open-label, parallel-group, investigator-initiated, international multicenter trial.SETTING & PARTICIPANTS: KTRs aged 18-80 years with a stable graft function (estimated glomerular filtration rate > 20 mL/min/1.73 m2), 3-60 months after transplantation, treated with tacrolimus or cyclosporine A, were eligible for inclusion.INTERVENTION: Continuation with a CNI-based regimen or switch to belatacept for 12 months.OUTCOMES: Comparison of the change in the estimated 7-year risk of major adverse CV events and all-cause mortality, changes in traditional markers of CV health, as well as measures of arterial stiffness.RESULTS: Among the 105 KTRs randomized, we found no differences between the treatment groups in the predicted risk for major adverse CV events or mortality. Diastolic blood pressure, measured both centrally by using a SphygmoCor device and peripherally, was lower after the belatacept treatment than after the CNI treatment. The mean changes in traditional cardiovascular (CV) risk factors, including kidney transplant function, were otherwise similar in both the treatment groups. The belatacept group had 4 acute rejection episodes; 2 were severe rejections, of which 1 led to graft loss.LIMITATIONS: The heterogeneous baseline estimated glomerular filtration rate and time from transplantation to trial enrollment in the participants. A limited study duration of 1 year.CONCLUSIONS: We found no effects on the calculated CV risk by switching to the belatacept treatment. Participants in the belatacept group had not only lower central and peripheral diastolic blood pressure but also a higher rejection rate.FUNDING: The trial has received a financial grant from Bristol-Myers Squibb.TRIAL REGISTRATION: EudraCT no. 2013-001178-20.
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| 4. |
- Dahle, Dag Olav, et al.
(författare)
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Inflammation-associated graft loss in renal transplant recipients
- 2011
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Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 1460-2385 .- 0931-0509. ; 26:11, s. 3756-3761
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Tidskriftsartikel (refereegranskat)abstract
- Background. Although short-term graft survival has improved substantially in renal transplant recipients, long-term graft survival has not improved over the last decades. The lack of knowledge of specific causes and risk factors has hampered improvements in long-term allograft survival. There is an uncertainty if inflammation is associated with late graft loss. Methods. We examined, in a large prospective trial, the inflammation markers high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) and their association with chronic graft dysfunction. We collected data from the Assessment of Lescol in Renal Transplant trial, which recruited 2102 maintenance renal transplant recipients. Results. Baseline values were hsCRP 3.8 +/- 6.7 mg/L and IL-6 2.9 +/- 1.9 pg/mL. Adjusted for traditional risk factors, hsCRP and IL-6 were independently associated with death-censored graft loss, the composite end points graft loss or death and doubling of serum creatinine, graft loss or death. Conclusion. The inflammation markers hsCRP and IL-6 are associated with long-term graft outcomes in renal transplant recipients.
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| 5. |
- Dahle, Dag Olav, et al.
(författare)
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Uric acid and clinical correlates of endothelial function in kidney transplant recipients
- 2014
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Ingår i: Clinical Transplantation. - : Wiley. - 0902-0063 .- 1399-0012. ; 28:10, s. 1167-1176
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Tidskriftsartikel (refereegranskat)abstract
- Uric acid is associated with increased mortality in kidney transplant recipients (KTRs), but it is uncertain if this involves endothelial dysfunction. We hypothesized, first, that there was an association between uric acid and endothelial function, and second, that there were associations between endothelial function and cardiac and mortality risk scores.METHODS: One hundred and fifty-two patients were examined 10 wk after kidney transplantation by two measures of endothelial function, the brachial artery flow-mediated dilatation (FMD) expressed as percent dilatation (FMD%), and fingertip peripheral arterial tone (PAT) expressed as log-reactive hyperemia index (LnRHI). Risk scores were calculated from a recently validated formula. Other clinical correlates of endothelial function were described in stepwise linear regression models.RESULTS: Uric acid was associated negatively with FMD% in an age- and gender-adjusted model, while not in the multivariable model. No association was shown between uric acid and LnRHI. FMD% was associated negatively with risk scores in both crude and age- and gender-adjusted models (p < 0.01). LnRHI was associated negatively with risk scores in the latter model only (p < 0.05).CONCLUSIONS: Uric acid was neither associated with FMD% nor LnRHI in KTRs. There were significant associations between endothelial function indices and cardiac and mortality risk scores.
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| 6. |
- de Gonzalo-Calvo, David, et al.
(författare)
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Improved cardiovascular risk prediction in patients with end-stage renal disease on hemodialysis using machine learning modeling and circulating microribonucleic acids
- 2020
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Ingår i: Theranostics. - : IVYSPRING INT PUBL. - 1838-7640. ; 10:19, s. 8665-8676
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: To test whether novel biomarkers, such as microribonucleic acids (miRNAs), and nonstandard predictive models, such as decision tree learning, provide useful information for medical decision-making in patients on hemodialysis (HD). Methods: Samples from patients with end-stage renal disease receiving HD included in the AURORA trial were investigated (n=810). The study included two independent phases: phase I (matched cases and controls, n=410) and phase II (unmatched cases and controls, n=400). The composite endpoint was cardiovascular death, nonfatal myocardial infarction or nonfatal stroke. miRNA quantification was performed using miRNA sequencing and RT-qPCR. The CART algorithm was used to construct regression tree models. A bagging-based procedure was used for validation. Results: In phase I, miRNA sequencing in a subset of samples (n=20) revealed miR-632 as a candidate (fold change=2.9). miR-632 was associated with the endpoint, even after adjusting for confounding factors (HR from 1.43 to 1.53). These findings were not reproduced in phase II. Regression tree models identified eight patient subgroups with specific risk patterns. miR-186-5p and miR-632 entered the tree by redefining two risk groups: patients older than 64 years and with hsCRP<0.827 mg/L and diabetic patients younger than 64 years. miRNAs improved the discrimination accuracy at the beginning of the follow-up (24 months) compared to the models without miRNAs (integrated AUC [iAUC]=0.71). Conclusions: The circulating miRNA profile complements conventional risk factors to identify specific cardiovascular risk patterns among patients receiving maintenance HD.
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| 7. |
- Drechsler, Christiane, et al.
(författare)
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Homoarginine and Clinical Outcomes in Renal Transplant Recipients : Results From the Assessment of Lescol in Renal Transplantation Study
- 2015
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 99:7, s. 1470-1476
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite improvements in kidney transplantation, complications, including cardiovascular morbidity and graft loss, contribute to reduced graft and patient survival. The amino acid homoarginine exerts a variety of beneficial effects that may be relevant for cardiovascular and graft outcomes, which is investigated in the present study.Methods: Homoarginine was measured in 829 renal transplant recipients participating in the placebo group of the Assessment of Lescol in Renal Transplantation study. Mean follow-up was 6.7 years. By Cox regression analyses, we determined hazard ratios (HRs) to reach prespecified, adjudicated endpoints according to baseline homoarginine levels: major adverse cardiovascular events (n = 103), cerebrovascular events (n = 53), graft failure or doubling of serum creatinine (n = 140), noncardiovascular mortality (n = 51), and all-cause mortality (n = 107).Results: Patients mean age was 50 ± 11 years, homoarginine concentration was 1.96 ± 0.76 µmol/L, and 65% were men. Patients in the lowest homoarginine quartile (<1.40 µmol/L) had an adjusted 2.6-fold higher risk of cerebrovascular events compared to those in the highest quartile (>2.34 µmol/L) (HR, 2.56; 95% confidence interval [95% CI], 1.13–5.82). Similarly, the renal endpoint occurred at a significantly increased rate in the lowest homoarginine quartile (HR, 2.34; 95% CI, 1.36–4.02). For noncardiovascular and all-cause mortality, there was also increased risk associated with the lowest levels of homoarginine, with HRs of 4.34 (95% CI, 1.63–10.69) and 2.50 (95% CI, 1.38–4.55), respectively.Conclusions: Low homoarginine is strongly associated with cerebrovascular events, graft loss and progression of kidney failure and mortality in renal transplant recipients. Whether interventions with homoarginine supplementation improve clinical outcomes requires further evaluation.
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| 8. |
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| 9. |
- Ekberg, Henrik, et al.
(författare)
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Clinicians underestimate gastrointestinal symptoms and overestimate quality of life in renal transplant recipients: A multinational survey of nephrologists
- 2007
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Ingår i: Transplantation. - 1534-6080. ; 84:8, s. 1052-1054
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Tidskriftsartikel (refereegranskat)abstract
- Gastrointestinal (GI) symptoms are common in renal transplant recipients and are associated with impaired health-related quality of life (HRQoL). We investigated clinician attitudes to GI symptoms and HRQoL in these patients by surveying 145 nephrologists from Sweden, Denmark, Finland, and Norway. In total, 79 clinicians responded. They estimated that 20% of their patients experienced GI discomfort and that 36% had impaired HRQoL. We previously conducted a survey of the renal transplant recipients treated-by-these clinicians, inwhich 92% reported troublesome GI symptoms and 53% had impaired HRQoL compared with the general population. Nephrologists were more likely to manage GI symptoms by reducing immunosuppressant dose (87%) than by switching medication to one with fewer GI side effects (66%). We conclude that clinicians appear to underestimate the prevalence of GI symptoms and impaired HRQoL. Improving patient-clinician communication could lead to more informed management, resulting in better HRQoL and increased graft survival.
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| 10. |
- Ekberg, Henrik, et al.
(författare)
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Increased prevalence of gastrointestinal symptoms associated with impaired quality of life in renal transplant recipients.
- 2007
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Ingår i: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 1534-6080 .- 0041-1337. ; 83:3, s. 282-289
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Tidskriftsartikel (refereegranskat)abstract
- Background. Immunosuppressive therapies have been associated with gastrointestinal (GI) side effects, which may impair health-related quality of life (HRQoL). Methods. In this survey, 4,232 renal transplant recipients from Denmark, Finland, Nor-way, and Sweden completed the Short-Form 36 (SF-36) questionnaire and the Gastrointestinal Symptom Rating Scale (GSRS). SF-36 scores were compared with country norm values. Multiple logistic regression analysis was used to identify immunosuppressants associated with GI symptoms. Results. The prevalence of troublesome GI symptoms (GSRS > 1) was 83% for indigestion, 69% for abdominal pain, 58% for constipation, 53% for diarrhea, 47% for reflux, and 92% for any GI symptom. Compared with the general population, HRQoL was most commonly meaningfully impaired in the general health dimension (53% of patients). The presence and severity of GI symptoms were associated with worse HRQoL. Tacrolimus showed a significant association with diarrhea (odds ratio [OR]: 1.7; 95% confidence interval [CI]: 1.4-2.0) and constipation (OR: 1.3; 95% Cl: 1.1-1.6), and sirolimus with indigestion (OR: 2.9; 95% Cl: 1.0-8.1) and abdominal pain (OR: 2.2; 95% Cl: 1.1-4.4). Conclusions. GI symptoms are associated with impaired HRQoL in the renal transplant population. Managing GI symptoms by careful choice of immunosuppressants should be a focus for improving HRQoL in renal transplant recipients
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| 11. |
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| 12. |
- Fellström, Bengt C., 1947-, et al.
(författare)
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Chronic allograft nepropathy
- 2009
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Ingår i: Evidence-based nephrology. - Oxford : Wiley-Blackwell. - 9781405139755 ; , s. 599-608
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 13. |
- Fellström, Bengt, et al.
(författare)
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Cardiovascular disease in patients with renal disease: the role of statins.
- 2009
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Ingår i: Current medical research and opinion. - : Informa Healthcare. - 1473-4877 .- 0300-7995. ; 25:1, s. 271-85
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Atherosclerosis is common in patients with chronic kidney disease (CKD), and cardiovascular disease (CVD) represents a major cause of death. The National Kidney Foundation guidelines favour the use of statin therapy for treatment of dyslipidaemia in patients with CKD. Much evidence supports statin therapy for reducing CVD and improving outcomes in the general population, but there is less evidence in patients with CKD. Consequently, prevention of CVD in CKD is based primarily on extrapolation from non-CKD trials. Significantly, in trials specifically designed to investigate patients with CKD, evidence is emerging for improved cardiovascular outcomes with statin therapy. This review describes available data relating to cardiovascular outcomes and the role of statins in patients with CKD, including pre-dialysis, dialysis, and renal transplant patients. RESEARCH DESIGN AND METHODS: The PubMed database was searched (1998-present) to ensure comprehensive identification of publications (including randomised clinical trials) relevant to CKD patients, patterns of cardiovascular outcome in such patients and their relationship to lipid profile, and the role of statins for the prevention and treatment of cardiovascular complications. RESULTS: There are conflicting data on the relationship between dyslipidaemia and cardiovascular outcomes, with one major study of statin therapy (4D--Deutsche Diabetes Dialyse Studie) providing equivocal results. Further studies, including AURORA (A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis: an Assessment of survival and cardiovascular events; NCT00240331) in patients receiving haemodialysis, and SHARP (Study of Heart And Renal Protection; NCT00125593) in patients with CKD including those on dialysis, should help to clarify the role of statin therapy in these populations. CONCLUSIONS: More studies are needed to elucidate the role of statins in improving cardiovascular outcomes for CKD patients. It is anticipated that ongoing clinical trials geared towards the optimal prevention and treatment of CVD in patients with CKD will help guide clinicians in the management of CKD.
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| 14. |
- Fellström, Bengt, et al.
(författare)
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Cardiovascular risk in renal transplantation
- 2008
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Ingår i: Trends in Transplantation. - 1887-455X. ; 2:2, s. 92-100
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Recension (övrigt vetenskapligt/konstnärligt)abstract
- Renal transplant patients suffer from a higher risk of cardiovascular morbidity and mortality. The risk-factor spectrum is different from the general population; several risk factors are transplantation specific, and to a large extent dependent on the immunosuppressive drugs used to prevent rejection. Due to the complexity of the risk factors, the variable impact of each factor on different cardiovascular outcomes and the inter-relationships between risk factors, it is difficult to judge the overall cardiovascular risk in a single renal transplant patient. In this paper we review risk-factor data from the literature, limited to single risk factors and their impact on single cardiovascular outcomes. We believe that a cardiovascular risk calculator specific to the renal transplant population, which takes into account all the important risk factors for a cardiovascular event, based upon a high quality database such as the ALERT data set, may provide a solid guidance to means to assess the overall cardiovascular risk in renal transplant recipients.
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| 15. |
- Fellström, Bengt, et al.
(författare)
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Effect of fluvastatin on renal end points in the Assessment of Lescol in Renal Transplant (ALERT) trial
- 2004
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Ingår i: Kidney International. - : Elsevier BV. - 0085-2538 .- 1523-1755. ; 66:4, s. 1549-1555
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hyperlipidemia is a risk factor for long-term renal transplant dysfunction, but no prospective clinical trials have investigated the effects of statin treatment on graft function in renal transplant recipients. The aim of the present study was to evaluate the effect of fluvastatin on long-term renal transplant function and development of chronic allograft nephropathy in the ALERT (Assessment of Lescol in Renal Transplantation) study. METHODS: ALERT was a randomized, double-blind, placebo-controlled study of the effect of fluvastatin, 40 mg and 80 mg daily, in renal transplant recipients. Patients were randomized to receive either fluvastatin (N= 1050) or placebo (N= 1052) and followed for five to six years. Renal end points included graft loss or doubling of serum creatinine or death; glomerular filtration rate (GFR) was also measured during follow-up in a subset of patients (N= 439). RESULTS: There were 283 patients (13.5%) with graft loss, mainly due to chronic rejection (82%), yielding an annual rate of 2.4%. Fluvastatin treatment significantly lowered mean low-density lipoprotein (LDL)-cholesterol levels by 32% (95% CI -33 to -30) compared with placebo, but had no significant effect on the incidence of renal graft loss or doubling of serum creatinine, or decline in GFR throughout follow-up in the whole study population. Neither was any treatment effect by fluvastatin found in any of the subgroups analyzed. CONCLUSION: Fluvastatin treatment significantly improves lipid values in renal transplant recipients but has no effect on graft loss or doubling of serum creatinine.
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| 16. |
- Fellström, Bengt, et al.
(författare)
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Effect of Rosuvastatin on Outcomes in Chronic Haemodialysis Patients : Baseline Data from the AURORA Study
- 2007
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Ingår i: Kidney and Blood Pressure Research. - : S. Karger AG. - 1420-4096 .- 1423-0143. ; 30:5, s. 314-322
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cardiovascular disease (CVD) is the leading cause of death in patients with end-stage renal disease (ESRD). Aims: AURORA (A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis: an Assessment of survival and cardiovascular events) is the first large-scale international trial to assess the effects of statins on cardiovascular outcomes in patients with ESRD on chronic haemodialysis. Preliminary baseline data from the randomised population are presented. Methods: A total of 2,775 patients from 280 centres in 25 countries were randomised into the study. Patients aged 50-80 years on regular chronic haemodialysis for at least 3 months before screening were eligible for inclusion. They were randomised 1:1 to receive either rosuvastatin 10 mg or placebo daily and assessed throughout the study. Results: The mean age at baseline was 64 years. Most patients were male (62%) and 85% were white. The median time since commencing renal replacement was 32 months. Mean total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels were 4.53 mmol/l (175 mg/dl) and 2.57 mmol/l (99 mg/dl), respectively. Conclusion: Results from the AURORA trial will impact on the current guidelines and use of statins in this patient population.
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| 17. |
- Fellström, Bengt, et al.
(författare)
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Effect of rosuvastatin on outcomes in chronic haemodialysis patients : design and rationale of the AURORA study
- 2005
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Ingår i: Current Controlled Trials. - : Springer Science and Business Media LLC. - 1468-6708 .- 1468-6694. ; 6:1, s. 9-16
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with end-stage renal disease (ESRD) are at high risk of cardiovascular events. Multiple risk factors for atherosclerosis are present in ESRD and may contribute to the increased risk of cardiovascular mortality in this population. In contrast to patients with normal renal function, the benefits of modifying lipid levels on cardiovascular outcomes in patients with ESRD on haemodialysis have yet to be confirmed in large prospective randomised trials. A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis: an Assessment of survival and cardiovascular events (AURORA) will be the first large-scale international trial to assess the effects of statin therapy on cardiovascular morbidity and mortality in ESRD patients on chronic haemodialysis. METHODS: More than 2,750 ESRD patients who have been receiving chronic haemodialysis treatment for at least 3 months have been randomised (1:1), irrespective of baseline lipid levels, to treatment with rosuvastatin 10 mg or placebo. The primary study endpoint is the time to a major cardiovascular event (first occurrence of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke). Secondary endpoints include all-cause mortality, major cardiovascular event-free survival time, time to cardiovascular death, time to non-cardiovascular death, cardiovascular interventions, tolerability of treatment and health economic costs per life-year saved. Study medication will be given until 620 subjects have experienced a major cardiovascular event. CONCLUSION: Our hypothesis is that results from AURORA will establish the clinical efficacy and tolerability of rosuvastatin in patients with ESRD receiving chronic haemodialysis and guide the optimal management of this expanding population.
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| 18. |
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| 19. |
- Fellström, Bengt, et al.
(författare)
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No detrimental effect on renal function during long-term use of fluvastatin in renal transplant recipients in the Assessment of Lescol in Renal Transplantation (ALERT) study
- 2006
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Ingår i: Clinical Transplantation. - : Wiley. - 0902-0063 .- 1399-0012. ; 20:6, s. 732-739
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Tidskriftsartikel (refereegranskat)abstract
- Background: Concerns have recently been raised regarding a potential harmful effect of statins on renal function. This study investigated the effect of fluvastatin treatment on renal function in renal transplant recipients enrolled in the Assessment of Lescol in Renal Transplantation (ALERT) trial. Methods: ALERT was a randomized, double-blind, placebo-controlled study of the effect of fluvastatin, 40-80 mg daily (n = 1050) or placebo (n = 1052) on cardiac and renal outcomes in renal transplant recipients over a follow-up period of five to six years. The incidence of graft loss, changes in serum creatinine, calculated creatinine clearance and proteinuria, and the incidence of renal adverse events (AEs) were assessed in both treatment groups. Results: Fluvastatin treatment in ALERT had no significant effect compared with placebo on renal function, assessed by serum creatinine (overall adjusted mean +/- SEM: fluvastatin, 175.4 +/- 2.20 mu mol/L; placebo, 172.7 +/- 2.20 mu mol/L; p = 0.39), creatinine clearance (fluvastatin, 55.3 +/- 0.30 mL/min; placebo, 55.8 +/- 0.30 mL/min; p = 0.26) or proteinuria (fluvastatin, 0.58 +/- 0.03 g/24 h; placebo, 0.53 +/- 0.03 g/24 h; p = 0.31). There were no significant differences between treatment groups when the 283 patients suffering graft loss were excluded from the analysis. Fluvastatin also had no detrimental effect on creatinine clearance or proteinuria in the subgroup of 340 diabetic patients without graft loss in ALERT. No notable differences in the rate of renal or musculoskeletal AEs were observed between fluvastatin and placebo groups. Conclusions: Fluvastatin had no detrimental effect on renal function, or the risk of renal AEs, in renal transplant recipients with or without diabetes enrolled in ALERT. Fluvastatin treatment for the prevention of cardiac events may therefore be used without fear of jeopardizing renal function.
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| 20. |
- Fellström, Bengt, 1947-, et al.
(författare)
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Renal dysfunction as a risk factor for mortality and cardiovascular disease in renal transplantation : experience from the Assessment of Lescol in Renal Transplantation trial
- 2005
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Ingår i: Transplantation. - : Lippincott, Williams and Wilkins. - 0041-1337 .- 1534-6080. ; 79:9, s. 1160-1163
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Renal-transplant recipients have shortened life expectancy primarily because of premature cardiovascular disease. Traditional and nontraditional risk factors for cardiovascular disease are prevalent in renal patients. In renal-transplant recipients, immunosuppressive therapy can be nephrotoxic and aggravate cardiovascular disease risk factors. Renal dysfunction has been established as a risk factor for cardiovascular disease and mortality in different populations. We evaluated the effects of baseline renal-transplant function on mortality and cardiovascular and renal endpoints in 1,052 placebo-treated patients of the Assessment of Lescol in Renal Transplantation trial. METHODS: All renal-transplant recipients were on cyclosporine-based immunosuppressive therapy. Follow-up was 5 to 6 years, and endpoints included cardiac death, noncardiovascular death, all-cause mortality, major adverse cardiac event (MACE), stroke, nonfatal myocardial infarction, and graft loss. RESULTS: Baseline serum creatinine was strongly and independently associated with increased cardiac, noncardiovascular, and all-cause mortality, as well as MACE and graft loss. Serum creatinine was not a risk factor for stroke or nonfatal myocardial infarction. CONCLUSIONS: Elevated baseline serum creatinine in renal-transplant recipients is a strong and independent risk factor for all-cause, noncardiovascular and cardiac mortality, MACE, and graft loss.
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| 21. |
- Fellström, Bengt, 1947-, et al.
(författare)
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Renal dysfunction is a strong and independent risk factor for mortality and cardiovascular complications in renal transplantation
- 2005
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Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135 .- 1600-6143. ; 5:8, s. 1986-1991
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Tidskriftsartikel (refereegranskat)abstract
- Renal transplant recipients (RTR) have shortened life expectancy, primarily due to premature cardiovascular disease (CVD). Traditional CVD risk factors are highly prevalent. In addition, several non-traditional risk factors may contribute to the high risk. The aim of the study was to evaluate the effects of renal dysfunction on mortality and cardiovascular complications in 1052 placebo-treated patients of the Assessment of LEscol in Renal Transplantation (ALERT) trial. Follow-up was 5-6 years and endpoints included cardiac death, non-cardiovascular death, all-cause mortality, major adverse cardiac event (MACE), non-fatal myocardial infarction (MI) and stroke. The effects of serum creatinine at baseline on these endpoints were evaluated. Elevated serum creatinine in RTR was a strong and independent risk factor for MACE, cardiac, non-cardiovascular, and all-cause mortality, but not for stroke or non-fatal MI alone. Serum creatinine was associated with increased mortality and MACE, independent of established CVD risk factors. Graft loss resulted in increased incidences of non-cardiovascular death, all-cause mortality, MACE and non-fatal MI. In conclusion, elevated serum creatinine is a strong risk factor for all-cause, non-cardiovascular and cardiac mortality, and MACE, independent of traditional risk factors, but not for stroke or non-fatal MI alone.
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| 22. |
- Fellström, Bengt, et al.
(författare)
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Rosuvastatin and cardiovascular events in patients undergoing hemodialysis.
- 2009
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Ingår i: The New England journal of medicine. - 1533-4406 .- 0028-4793. ; 360:14, s. 1395-407
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Statins reduce the incidence of cardiovascular events in patients at high cardiovascular risk. However, a benefit of statins in such patients who are undergoing hemodialysis has not been proved. METHODS: We conducted an international, multicenter, randomized, double-blind, prospective trial involving 2776 patients, 50 to 80 years of age, who were undergoing maintenance hemodialysis. We randomly assigned patients to receive rosuvastatin, 10 mg daily, or placebo. The combined primary end point was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Secondary end points included death from all causes and individual cardiac and vascular events. RESULTS: After 3 months, the mean reduction in low-density lipoprotein (LDL) cholesterol levels was 43% in patients receiving rosuvastatin, from a mean baseline level of 100 mg per deciliter (2.6 mmol per liter). During a median follow-up period of 3.8 years, 396 patients in the rosuvastatin group and 408 patients in the placebo group reached the primary end point (9.2 and 9.5 events per 100 patient-years, respectively; hazard ratio for the combined end point in the rosuvastatin group vs. the placebo group, 0.96; 95% confidence interval [CI], 0.84 to 1.11; P=0.59). Rosuvastatin had no effect on individual components of the primary end point. There was also no significant effect on all-cause mortality (13.5 vs. 14.0 events per 100 patient-years; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P=0.51). CONCLUSIONS: In patients undergoing hemodialysis, the initiation of treatment with rosuvastatin lowered the LDL cholesterol level but had no significant effect on the composite primary end point of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. (ClinicalTrials.gov number, NCT00240331.)
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| 23. |
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| 24. |
- Girerd, Sophie, et al.
(författare)
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Arteriovenous fistula thrombosis is associated with increased all-cause and cardiovascular mortar in haemodialysis patients from the AURORA trial
- 2020
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Ingår i: Clinical Kidney Journal. - : Oxford University Press (OUP). - 2048-8505 .- 2048-8513. ; 13:1, s. 116-122
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Tidskriftsartikel (refereegranskat)abstract
- Background. The impact of arteriovenous fistula (AVF) or graft (AVG) thrombosis on mortality has been sparsely studied. This study investigated the association between AVF/AVG thrombosis and all-cause and cardiovascular mortality.Methods. The data from 2439 patients with AVF or AVG undergoing maintenance haemodialysis (HD) included in the A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events trial (AURORA) were analysed using a time-dependent Cox model. The incidence of vascular access (VA) thrombosis was a pre-specified secondary outcome.Results. During follow-up, 278 AVF and 94 AVG thromboses were documented. VA was restored at 22 +/- 64 days after thrombosis (27 patients had no restoration with subsequent permanent central catheter). In multivariable survival analysis adjusted for potential confounders, the occurrence of AVF/AVG thrombosis was associated with increased early and late allcause mortality, with a more pronounced association with early all-cause mortality {hazard ratio [HR] < 90 days 2.70 [95% confidence interval (CI) 1.83-3.97], P < 0.001; HR > 90 days 1.47 [1.20-1.80], P < 0.001). In addition, the occurrence of AVF thrombosis was significantly associated with higher all-cause mortality, whether VA was restored within 7 days [HR 1.34 (95% CI 1.02-1.75), P = 0.036] or later than 7 days [HR 1.81 (95% CI 1.29-2.53), P = 0.001].Conclusions. AVF/AVG thrombosis should be considered as a major clinical event since it is strongly associated with increased mortality in patients on maintenance HD, especially in the first 90 days after the event and when access restoration occurs >7 days after thrombosis. Clinicians should pay particular attention to the timing of VA restoration and the management of these patients during this high-risk period. The potential benefit of targeting overall patient risk with more aggressive treatment after AVF/AVG restoration should be further explored.
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| 25. |
- Herrington, William, et al.
(författare)
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Impact of renal function on the effects of LDL cholesterol lowering with statin-based regimens : a meta-analysis of individual participant data from 28 randomised trials
- 2016
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Ingår i: The Lancet Diabetes and Endocrinology. - 2213-8587 .- 2213-8595. ; 4:10, s. 829-839
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Statin therapy is effective for the prevention of coronary heart disease and stroke in patients with mild-to-moderate chronic kidney disease, but its effects in individuals with more advanced disease, particularly those undergoing dialysis, are uncertain.METHODS: We did a meta-analysis of individual participant data from 28 trials (n=183 419), examining effects of statin-based therapy on major vascular events (major coronary event [non-fatal myocardial infarction or coronary death], stroke, or coronary revascularisation) and cause-specific mortality. Participants were subdivided into categories of estimated glomerular filtration rate (eGFR) at baseline. Treatment effects were estimated with rate ratio (RR) per mmol/L reduction in LDL cholesterol.FINDINGS: Overall, statin-based therapy reduced the risk of a first major vascular event by 21% (RR 0·79, 95% CI 0·77-0·81; p<0·0001) per mmol/L reduction in LDL cholesterol. Smaller relative effects on major vascular events were observed as eGFR declined (p=0·008 for trend; RR 0·78, 99% CI 0·75-0·82 for eGFR ≥60 mL/min per 1·73 m(2); 0·76, 0·70-0·81 for eGFR 45 to <60 mL/min per 1·73 m(2); 0·85, 0·75-0·96 for eGFR 30 to <45 mL/min per 1·73 m(2); 0·85, 0·71-1·02 for eGFR <30 mL/min per 1·73 m(2) and not on dialysis; and 0·94, 0·79-1·11 for patients on dialysis). Analogous trends by baseline renal function were seen for major coronary events (p=0·01 for trend) and vascular mortality (p=0·03 for trend), but there was no significant trend for coronary revascularisation (p=0·90). Reducing LDL cholesterol with statin-based therapy had no effect on non-vascular mortality, irrespective of eGFR.INTERPRETATION: Even after allowing for the smaller reductions in LDL cholesterol achieved by patients with more advanced chronic kidney disease, and for differences in outcome definitions between dialysis trials, the relative reductions in major vascular events observed with statin-based treatment became smaller as eGFR declined, with little evidence of benefit in patients on dialysis. In patients with chronic kidney disease, statin-based regimens should be chosen to maximise the absolute reduction in LDL cholesterol to achieve the largest treatment benefits.FUNDING: UK Medical Research Council, British Heart Foundation, Cancer Research UK, European Community Biomed Programme, Australian National Health and Medical Research Council, Australian National Heart Foundation.
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| 26. |
- Holdaas, Hallvard, et al.
(författare)
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Beneficial effect of early initiation of lipid-lowering therapy following renal transplantation
- 2005
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Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 20:5, s. 974-980
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Renal transplant recipients have a significantly reduced life expectancy, largely due to premature cardiovascular disease. The aim of the current analysis was to investigate the importance of time of initiation of therapy after transplantation, on the benefits of statin therapy. METHODS: 2102 renal transplant recipients with total cholesterol levels of 4.0-9.0 mmol/l were randomly assigned to treatment with fluvastatin (n = 1050) or placebo (n = 1052) and followed for a mean time of 5.1 years. The end-points were major cardiac events. The average median time from transplantation to randomization was 4.5 years (range: 0.5-29 years). RESULTS: In patients starting treatment with fluvastatin <4.5 years after renal transplantation, the incidence of cardiac events was 4.6% over 5.1 years vs 9.2% in those on placebo (P = 0.007). Fluvastatin significantly reduced the risk of cardiac death and non-fatal myocardial infarction by 56% [risk ratio (RR): 0.44; 95% confidence interval (95% CI): 0.26-0.74; P = 0.002]. In a more detailed analysis patients were grouped into 2-year intervals (since the last transplantation). The frequency of cardiac death and non-fatal myocardial infarction was reduced by 3.2%, 5.1%, 9.6% and 8.2% with fluvastatin treatment as compared to 6%, 10.4%, 13.4% and 9.6% with placebo when treatment was initiated at 0-2, 2-4, 4-6 and >6 years, respectively. The risk reduction for patients initiating therapy with fluvastatin at years 0-2 (compared with >6 years) following transplantation was 59% (RR: 0.41; 95% CI: 0.18-0.92; P = 0.0328). This is also reflected in total time on renal replacement therapy: in patients in the first quartile (<47 months) fluvastatin use was associated with a risk reduction of 64% compared with 19% for patients in the fourth quartile (>120 months) (P = 0.033). CONCLUSIONS: Our data support an early introduction of fluvastatin therapy in a population of transplant recipients at high risk of premature coronary heart disease.
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| 27. |
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| 28. |
- Holdaas, Hallvard, et al.
(författare)
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Conversion of Long-Term Kidney Transplant Recipients From Calcineurin Inhibitor Therapy to Everolimus : A Randomized, Multicenter, 24-Month Study
- 2011
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 92:4, s. 410-418
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Tidskriftsartikel (refereegranskat)abstract
- Background. Benefits of conversion from calcineurin inhibitor (CNI) to mammalian target of rapamycin inhibitor-based immunosuppression in long-term kidney transplant patients remain uncertain. Methods. ASCERTAIN was a 24-month, open-label, multicenter study. Kidney transplant patients more than 6 months posttransplant receiving CNI (baseline glomerular filtration rate [GFR] 30-70 mL/min/1.73 m(2)) were randomized to everolimus with CNI elimination (n = 127) or CNI minimization (n = 144), or continued CNI unchanged (controls, n = 123) to assess the effect on measured GFR at month 24 after randomization. Results. Renal function was stable in all groups to month 24. Mean measured GFR at month 24, the primary endpoint, was 48.0 +/- 22.0 mL/min/1.73 m(2), 46.6 +/- 21.1 mL/min/1.73 m(2), and 46.0 +/- 20.4 mL/min/1.73 m(2) in the CNI elimination, CNI minimization, and control groups, respectively. Differences between CNI elimination (1.12 mL/min/1.73 m(2), 95% confidence interval [CI] -3.51 to 5.76, P=0.63) and CNI minimization (0.59 mL/min/1.73 m(2), 95% CI -3.88 to 5.07, P=0.79) versus controls at month 24 were nonsignificant that is, the primary endpoint was not met. No efficacy endpoint differed significantly between groups. Post hoc analyses showed that patients with baseline creatinine clearance (CrCl) more than 50 mL/min had a significantly greater increase in measured GFR after CNI elimination versus controls (difference 11.4 mL/min/1.73 m(2), 95% CI 2.1 to 20.8 mL/min/1.73 m(2), P=0.017). Adverse events resulted in discontinuation in 36 (28.3%) CNI elimination patients, 24 (16.7%) CNI minimization patients, and 5 (4.1%) controls (P<0.001 vs. CNI elimination; P=0.020 vs. CNI minimization). Conclusion. Conversion to everolimus with CNI elimination or minimization a mean of 5.6 years after kidney transplantation had no overall renal benefit and was associated with more frequent adverse events and discontinuations. Patients with CrCl more than 50 mL/min may benefit from a change in therapy more than 6 months after renal transplantation.
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| 29. |
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| 30. |
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| 31. |
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| 32. |
- Holdaas, Hallvard, et al.
(författare)
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Rosuvastatin in Diabetic Hemodialysis Patients
- 2011
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 22:7, s. 1335-1341
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Tidskriftsartikel (refereegranskat)abstract
- A randomized, placebo-controlled trial in diabetic patients receiving hemodialysis showed no effect of atorvastatin on a composite cardiovascular endpoint, but analysis of the component cardiac endpoints suggested that atorvastatin may significantly reduce risk. Because the AURORA (A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events) trial included patients with and without diabetes, we conducted a post hoc analysis to determine whether rosuvastatin might reduce the risk of cardiac events in diabetic patients receiving hemodialysis. Among the 7:31 participants with diabetes, traditional risk factors such as LDL-C, smoking, and BP did not associate with cardiac events (cardiac death and nonfatal myocardial infarction). At baseline, only age and high-sensitivity C-reactive protein were independent risk factors for cardiac events. Assignment to rosuvastatin associated with a nonsignificant 16.2% reduction in risk for the AURORA trial's composite primary endpoint of cardiac death, nonfatal MI, or fatal or nonfatal stroke (HR 0.84; 95% CI 0.65 to 1.07). There was no difference in overall stroke, but the rosuvastatin group had more hemorrhagic strokes than the placebo group (12 versus two strokes, respectively; HR, 5.21; 95% CI 1.17 to 23.27). Rosuvastatin treatment significantly reduced the rates of cardiac events by 32% among patients with diabetes (HR 0.68; 95% CI 0.51 to 0.90). In conclusion, among hemodialysis patients with diabetes mellitus, rosuvastatin might reduce the risk of fatal and nonfatal cardiac events.
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| 33. |
- Holme, Ingar, et al.
(författare)
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Model Comparisons of Competing Risk and Recurrent Events for Graft Failure in Renal Transplant Recipients
- 2013
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Ingår i: American Society of Nephrology. Clinical Journal. - 1555-9041 .- 1555-905X. ; 8:2, s. 241-247
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Tidskriftsartikel (refereegranskat)abstract
- Background and objectives Risk factor analysis of long-term graft survival in kidney transplant recipients is usually based on Cox regression models of time to first occurrence of doubling of serum creatinine or graft loss (DSCGL). However, death is a competing cause of failure, and censoring patients who die could bias estimates. We therefore compared estimates of time to first event versus estimates that included death as a competing risk and recurrent events. Design, setting, participants, & measurements A Cox regression analysis of 1997-2002 data from the Assessment of Lescol in Renal Transplant (ALERT) trial population identified an eight-factor risk model, by analyzing time to first occurrence of DSCGL. The same factors were re-analyzed, allowing for death as competing. The probability of survival free of DSCGL was estimated; and two recurrent models (marginal and conditional) were used for time to events. Results Creatinine, systolic BP, and HLA-DR mismatches lost 33%-46% of their strength of association with DSCGL when death was included as a competing risk. Small changes were observed if recurrent events were analyzed in the marginal model. Conclusion The relationship between serum creatinine and DSCGL was attenuated when death was considered as a competing risk; inclusion of recurrent events had little effect. These findings have important implications for analysis and trial design in populations at high mortality risk.
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| 34. |
- Jardine, Alan G., et al.
(författare)
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Cardiovascular risk and renal transplantation : post hoc analyses of the Assessment of Lescol in Renal Transplantation (ALERT) Study
- 2005
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Ingår i: American Journal of Kidney Diseases. - : Elsevier BV. - 0272-6386 .- 1523-6838. ; 46:3, s. 529-36
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Renal transplantation is associated with an increased risk for premature cardiovascular disease. We analyzed the data in the placebo arm of Assessment of Lescol in Renal Transplantation (ALERT) to improve our understanding of the relationship between cardiovascular risk factors and outcomes in this unique population. METHODS: We performed Cox survival analysis for myocardial infarction, cardiac death, and noncardiac death in 1,052 patients recruited to the placebo arm of ALERT. These subjects were aged 30 to 75 years, had stable graft function at least 6 months after transplantation, had a serum total cholesterol level between 155 and 348 mg/dL (4 and 9 mmol/L), and were receiving cyclosporine-based immunosuppression. RESULTS: The results confirm previous studies. In multivariate analysis, preexisting coronary heart disease (hazard ratio [HR], 3.69; P < 0.001), total cholesterol level (HR, 1.55 per 50 mg/dL; P = 0.0045), and prior acute rejection (HR, 2.36; P = 0.0023) were independent risk factors. Conversely, independent risk factors for cardiac death were age (HR, 1.58 per decade; P = 0.0033), diabetes (HR, 3.35; P = 0.0002), ST-T changes on the ECG (HR, 3.17; P = 0.0004), and serum creatinine level (HR, 2.65 per milligram per deciliter; P < 0.0001). CONCLUSION: This analysis confirms that renal transplant recipients share risk factors for myocardial infarction and cardiac death with the general population. However, the pattern of risk factors and their relationship with outcomes is atypical, highlighting the unique nature of cardiovascular risk in transplant recipients.
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| 35. |
- Jardine, Alan G., et al.
(författare)
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Fluvastatin prevents cardiac death and myocardial infarction in renal transplant recipients : post-hoc subgroup analyses of the ALERT Study
- 2004
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Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135 .- 1600-6143. ; 4:6, s. 988-995
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Tidskriftsartikel (refereegranskat)abstract
- Renal transplant recipients have a greatly increased risk of premature cardiovascular disease. The ALERT study was a multicenter, randomized, double-blind, placebo-controlled trial of fluvastatin (40-80 mg/day) in 2102 renal transplant recipients followed for 5-6 years. The main study used a composite cardiac end-point including myocardial infarction, cardiac death and cardiac interventions. Although reduced by fluvastatin, this primary end-point failed to achieve statistical significance thus precluding analysis of predefined subgroups. Therefore, in the present survival analysis, we used an alternative primary end-point of cardiac death or definite nonfatal myocardial infarction (as used in other cardiac outcome trials) which was significantly reduced by Fluvastatin therapy and permits subgroup analysis. Fluvastatin reduced LDL-cholesterol by 1 mmol/L compared with placebo, and the incidence of cardiac death or definite myocardial infarction was reduced from 104 to 70 events (RR 0.65; 95% CI 0.48, 0.88; p = 0.005). Fluvastatin use was associated with reduction in cardiac death or nonfatal myocardial infarction, which achieved statistical significance in many subgroups. The subgroups included patients at lower cardiovascular risk, who were younger, nondiabetic, nonsmokers and without pre-existing CVD. These data support the early introduction of statins following renal transplantation.
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| 36. |
- Jardine, Alan G., et al.
(författare)
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Organ Transplantation 2 : Prevention of cardiovascular disease in adult recipients of kidney transplants
- 2011
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 378:9800, s. 1419-1427
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Tidskriftsartikel (refereegranskat)abstract
- Although advances in immunosuppression, tissue typing, surgery, and medical management have made transplantation a routine and preferred treatment for patients with irreversible renal failure, successful transplant recipients have a greatly increased risk of premature mortality because of cardiovascular disease and malignancy compared with the general population. Conventional cardiovascular risk factors such as hyperlipidaemia, hypertension, and diabetes are common in transplant recipients, partly because of the effects of immunosuppressive drugs, and are associated with adverse outcomes. However, the natural history of cardiovascular disease in such recipients differs from that in the general population, and only statin therapy has been studied in a large-scale interventional trial. Thus, the management of this disease and the balance between management of conventional risk factors and modification of immunosuppression is complex.
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| 37. |
- Klaasen, Rolf Anton, et al.
(författare)
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A Fully Automated Method for the Determination of Serum Belatacept and Its Application in a Pharmacokinetic Investigation in Renal Transplant Recipients
- 2019
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Ingår i: Therapeutic Drug Monitoring. - : LIPPINCOTT WILLIAMS & WILKINS. - 0163-4356 .- 1536-3694. ; 41:1, s. 11-18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Belatacept (Nulojix; Bristol-Myers Squibb, New York, NY) is a biological immunosuppressive drug used for the prophylaxis of acute rejection after renal transplantation. Few studies have described belatacept pharmacokinetics, and the effect of therapeutic drug monitoring has not been investigated. We have developed a drug-capture assay (using drug target) to measure belatacept in serum and applied this assay in a pharmacokinetic study in renal transplant recipients. Methods: CD80 was used to trap belatacept onto streptavidin-coated wells. Captured drug was quantified using Eu3+-labeled protein A and time-resolved fluorescence. The assay was applied in a pilot pharmacokinetic study in renal transplanted patients receiving belatacept infusions. Belatacept serum concentrations were determined at several time points between belatacept infusions. A simple population pharmacokinetic model was developed to visualize measured and predicted belatacept serum concentrations. Results: The assay range was 0.9-30 mg/L with accuracy within 91%-99% and coefficients of variation ranging from 1.2% to 3.6%. Predilution extended the measurement range to 130 mg/L with an accuracy of 90% and coefficients of variation of 3.8%. Samples were stable during storage at 48 degrees C for 15 days and during 2 freeze-thaw cycles. Belatacept concentrations were determined in a total of 203 serum samples collected during 26 infusion intervals from 5 renal transplant recipients. The population pharmacokinetic model visualized both measured and predicted concentrations. Conclusions: We have developed an automated, accurate, and precise assay for the determination of belatacept serum concentrations. The assay was successfully applied in a pharmacokinetic study in renal transplant recipients receiving belatacept infusions.
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| 38. |
- Linde, Torbjörn, et al.
(författare)
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The use of pretransplant erythropoietin to normalize hemoglobin levels has no deleterious effects on renal transplantation outcome
- 2001
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Ingår i: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 0041-1337 .- 1534-6080. ; 71:1, s. 79-82
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of this study was to establish the outcome of renal transplantation in patients given pretransplant erythropoietin (EPO) treatment targeted at reaching a normal hemoglobin concentration (Hb), compared to those given EPO-treatment aimed at maintaining subnormal Hb. METHODS: A total of 416 patients from Scandinavian countries and with renal anaemia were enrolled to examine the effects of increasing Hb from a subnormal level (90-120 g/liter) to a normal level (135-160 g/liter) by EPO treatment. Half of the patients were randomized to have their Hb increased, with the other half randomized to maintain a subnormal Hb. Thirty-two patients from the normal Hb group and 24 patients from the subnormal group received a renal graft during the study period. The outcomes of these transplantations were examined prospectively for 6 months. RESULTS: Preoperative Hb levels were 143+/-17 and 121+/-14 g/liter in the two groups, respectively (P<0.0001). The Hb remained higher in the normal Hb group during the first 2 weeks after transplantation. The percentage of patients requiring postoperative blood transfusions in the normal Hb group was 16%, compared with 50% in the subnormal group (P<0.01). No statistically significant difference in the proportion of functioning grafts or in the serum creatinine levels could be detected. No correlation between EPO treatment and creatinine levels after transplantation was found. The frequency of adverse events was similar in the two groups. CONCLUSIONS: EPO treatment aimed at reaching a normal Hb in renal transplant recipients reduces the postoperative requirement for blood transfusions and has no deleterious effects on kidney graft function.
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| 39. |
- Mafham, Marion M, et al.
(författare)
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Prognostic utility of estimated albumin excretion rate in chronic kidney disease : results from the Study of Heart and Renal Protection
- 2018
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Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press. - 0931-0509 .- 1460-2385. ; 33:2, s. 257-264
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Tidskriftsartikel (refereegranskat)abstract
- Background: Estimated albumin excretion rate (eAER) provides a better estimate of 24-h albuminuria than albumin:creatinine ratio (ACR). However, whether eAER is superior to ACR in predicting end-stage renal disease (ESRD), vascular events (VEs) or death is uncertain.Methods: The prognostic utility of ACR and eAER (estimated from ACR, sex, age and race) to predict mortality, ESRD and VEs was compared using Cox proportional hazards regression among 5552 participants with chronic kidney disease in the Study of Heart and Renal Protection, who were not on dialysis at baseline.Results: During a median follow-up of 4.8 years, 1959 participants developed ESRD, 1204 had a VE and 1130 died (641 from a non-vascular, 369 from a vascular and 120 from an unknown cause). After adjustment for age, sex and eGFR, both ACR and eAER were strongly and similarly associated with ESRD risk. The average relative risk (RR) per 10-fold higher level was 2.70 (95% confidence interval 2.45-2.98) for ACR and 2.67 (2.43-2.94) for eAER. Neither ACR nor eAER provided any additional prognostic information for ESRD risk over and above the other. For VEs, there were modest positive associations between both ACR and eAER and risk [adjusted RR per 10-fold higher level 1.37 (1.22-1.53) for ACR and 1.36 (1.22-1.52) for eAER]. Again, neither measure added prognostic information over and above the other. Similar results were observed when ACR and eAER were related to vascular mortality [RR per 10-fold higher level: 1.64 (1.33-2.03) and 1.62 (1.32-2.00), respectively] or to non-vascular mortality [1.53 (1.31-1.79) and 1.50 (1.29-1.76), respectively].Conclusions: In this study, eAER did not improve risk prediction of ESRD, VEs or mortality.
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| 40. |
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| 41. |
- Mjörnstedt, Lars, 1956, et al.
(författare)
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Renal function three years after early conversion from a calcineurin inhibitor to everolimus : results from a randomized trial in kidney transplantation
- 2015
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Ingår i: Transplant International. - : Frontiers Media SA. - 0934-0874 .- 1432-2277. ; 28:1, s. 42-51
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Tidskriftsartikel (refereegranskat)abstract
- In a 36-month, open-label, multicenter trial, 202 kidney transplant recipients were randomized at week 7 post-transplant to convert to everolimus or remain on cyclosporine: 182 were analyzed to month 36 (92 everolimus, 90 controls). Mean (SD) change in measured GFR (mGFR) from randomization to month 36 was 1.3 (14.0)ml/min with everolimus versus -1.7 (15.4)ml/min in controls (P=0.210). In patients who remained on treatment, mean mGFR improved from randomization to month 36 by 7.9 (11.5)ml/min with everolimus (n=37) but decreased by 1.4 (14.7)ml/min in controls (n=62) (P=0.001). During months 12-36, death-censored graft survival was 100%, patient survival was 98.9% and 96.7% in the everolimus and control groups, respectively, and 13.0% and 11.1% of everolimus and control patients, respectively, experienced mild biopsy-proven acute rejection (BPAR). Protocol biopsies in a limited number of on-treatment patients showed similar interstitial fibrosis progression. Donor-specific antibodies were present at month 36 in 6.3% (2/32) and 18.0% (9/50) of on-treatment everolimus and control patients with available data (P=0.281). During months 12-36, adverse events were comparable, but discontinuation was more frequent with everolimus (33.7% vs. 10.0%). Conversion from cyclosporine to everolimus at 7weeks post-transplant was associated with a significant benefit in renal function at 3years when everolimus was continued.
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| 42. |
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| 43. |
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| 44. |
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| 45. |
- Norby, Gudrun Elisabeth, et al.
(författare)
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Effect of fluvastatin on cardiac outcomes in kidney transplant patients with systemic lupus erythematosus : a randomized placebo-controlled study
- 2009
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 60:4, s. 1060-1064
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Patients with systemic lupus erythematosus (SLE), with or without end-stage renal failure, are at increased risk of premature cardiovascular disease. Although statin therapy has been found to reduce cardiovascular risk in the general population, its effectiveness in kidney transplant recipients with SLE has not been examined. This study was undertaken to investigate the effect of fluvastatin on cardiac end points in a randomized controlled trial of renal transplant patients with SLE. METHODS: Patients with SLE were identified from among participants in the Assessment of Lescol in Renal Transplantation trial, a randomized, double-blind, placebo-controlled study of the effect of fluvastatin (40-80 mg/day) on cardiovascular outcomes in renal transplant recipients. Patients were randomized to either a group receiving fluvastatin or a placebo group for the duration of the 5-6-year trial, and then invited to continue in a 2-year open-label extension during which all participants, regardless of original group, received fluvastatin. Patients were followed up for a total of 7-8 years for assessment of the primary end point of major cardiac events, comprising nonfatal myocardial infarction, cardiac death, and coronary intervention procedures. RESULTS: Fluvastatin reduced low-density lipoprotein cholesterol levels by 29.2% (95% confidence interval [95% CI] 18.3-40%), from a mean +/- SD of 4.0 +/- 0.9 mmoles/liter to 2.8 +/- 1.1 mmoles/liter, and total cholesterol by 19.6% (95% CI 11.7-27.5%), from 6.4 +/- 0.9 mmoles/liter to 5.1 +/- 1.1 mmoles/liter. Compared with placebo-treated patients, patients randomized to receive fluvastatin exhibited a 73.4% reduction in the risk of major cardiac events (relative risk 26.6 [95% CI 5.9-119.4], P = 0.064). CONCLUSION: Our results indicate that the effect of fluvastatin on cardiac events in renal transplant recipients with SLE is similar to that observed with statin therapy in the renal transplant population as a whole.
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| 46. |
- Oien, Cecilia Montgomery, et al.
(författare)
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Gender-associated risk factors for cardiac end points and total mortality after renal transplantation : post hoc analysis of the ALERT study
- 2006
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Ingår i: Clinical Transplantation. - : Wiley. - 0902-0063 .- 1399-0012. ; 20:3, s. 374-82
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Female gender offers a cardioprotective effect over men in the general population, but is lost in the dialysis population. Whether renal transplantation restores the gender-dependent cardiac protection and whether there is a difference in the impact of risk factors is not known. METHODS: This is a post hoc analysis of pre-defined end points in the placebo arm in the Assessment of Lescol in Renal Transplantation (ALERT) study, a study in renal transplant recipients. Cox regression was performed to estimate the association between different risk factors at baseline and non-fatal myocardial infarction (MI) or cardiac death and total mortality, and specifically assess whether there are gender differences. RESULTS: The placebo arm included 1052 patients (mean age 50.1 +/- 11.1 yr, 65.3% males) with a mean follow-up of 65 months. The incidence of non-fatal MI or cardiac death was 10.9% vs. 7.9% (NS) and total mortality 13.3% vs. 12.8% (NS) in men and women. In multivariate analysis, previous coronary heart disease (CHD), diabetes, treatment for rejection and serum triglycerides were predictive for cardiac events in men, and low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio only in women. A slightly different risk-factor pattern appeared for total mortality. Diabetes, ECG abnormalities, plasma triglycerides, serum creatinine, time on dialysis and age predicted total mortality in men, while ECG abnormalities, LDL/HDL ratio and age were predictors in women. CONCLUSION: In this relatively low-risk population of renal transplant recipients, no gender difference in cardiac events or total mortality was observed, suggesting that female gender advantage regarding CHD is not restored following transplantation. The predictive value of risk factors differed in men and women.
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| 47. |
- Pihlstrom, Hege, et al.
(författare)
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Increased Risk of All-Cause Mortality and Renal Graft Loss in Stable Renal Transplant Recipients With Hyperparathyroidism
- 2015
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 99:2, s. 351-359
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Tidskriftsartikel (refereegranskat)abstract
- Background. Hyperparathyroidism is reported in 10% to 66% of renal transplant recipients (RTR). The influence of persisting hyperparathyroidism on long-term clinical outcomes in RTR has not been examined in a large prospective study. Methods. We investigated the association between baseline parathyroid hormone (PTH) levels and major cardiovascular events, renal graft loss, and all-cause mortality by Cox Proportional Hazard survival analyses in 1840 stable RTR derived from the Assessment of LEscol in Renal Transplantation trial. Patients were recruited in a mean of 5.1 years after transplantation, and follow-up time was 6 to 7 years. Results. Significant associations between PTH and all 3 outcomes were found in univariate analyses. When adjusting for a range of plausible confounders, including measures of renal function and serum mineral levels, PTH remained significantly associated with all-cause mortality (4% increased risk per 10 units; P = 0.004), and with graft loss (6% increased risk per 10 units; P < 0.001), but not with major cardiovascular events. Parathyroid hormone above the upper limit of normal (65 pg/mL) indicated a 46% (P = 0.006) higher risk of death and an 85% higher risk of graft loss (P < 0.001) compared with low/normal values. Conclusions. Hyperparathyroidismis an independent, potentially remediable, risk factor for renal graft loss and all-cause mortality in RTR.
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| 48. |
- Pihlstrom, Hege, et al.
(författare)
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Symmetric Dimethylarginine as Predictor of Graft loss and All-Cause Mortality in Renal Transplant Recipients
- 2014
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Ingår i: Transplantation. - 0041-1337 .- 1534-6080. ; 98:11, s. 1219-1225
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Elevated symmetric dimethylarginine (SDMA) has been shown to predict cardiovascular events and all cause mortality in diverse populations. The potential role of SDMA as a risk marker in renal transplant recipients (RTR) has not been investigated. METHODS: We analyzed SDMA in the placebo arm of the Assessment of Lescol in Renal Transplantation study, a randomized controlled trial of fluvastatin in RTR. Mean follow-up was 5.1 years. Patients were grouped into quartiles based on SDMA levels at study inclusion. Relationships between SDMA and traditional risk factors for graft function and all-cause mortality were analyzed in 925 RTR using univariate and multivariate survival analyses. RESULTS: In univariate analysis, SDMA was significantly associated with renal graft loss, all-cause death, and major cardiovascular events. After adjustment for established risk factors including estimated glomerular filtration rate, an elevated SDMA-level (4th quartile, >1.38 mumol/L) was associated with renal graft loss; hazard ratio (HR), 5.51; 95% confidence interval (CI), 1.95-15.57; P=0.001, compared to the 1st quartile. Similarly, SDMA in the 4th quartile was independently associated with all-cause mortality (HR, 4.56; 95% CI, 2.15-9.71; P<0.001), and there was a strong borderline significant trend for an association with cardiovascular mortality (HR, 2.86; 95% CI, 0.99-8.21; P=0.051). CONCLUSION: In stable RTR, an elevated SDMA level is independently associated with increased risk of all-cause mortality and renal graft loss.
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| 49. |
- Pihlstrøm, Hege K, et al.
(författare)
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Genetic markers associated with long term cardiovascular outcome in kidney transplant recipients
- 2019
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Ingår i: American Journal of Transplantation. - : John Wiley & Sons. - 1600-6135 .- 1600-6143. ; 19:5, s. 1444-1451
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Tidskriftsartikel (refereegranskat)abstract
- There is a clear genetic contribution to the risk of cardiovascular diseases, and a composite genetic risk score (GRS) based on 27 single nucleotide polymorphisms (SNPs) was reported to predict risk of cardiovascular events in the general population. We aimed to evaluate this risk score in renal transplant recipients, a population with heightened cardiovascular risk, with a yet unknown genetic contribution. This article is protected by copyright. All rights reserved.
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| 50. |
- Schjelderup, Patrick, et al.
(författare)
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Anemia is a predictor of graft loss but not cardiovascular events and all-cause mortality in renal transplant recipients : follow-up data from the ALERT study
- 2013
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Ingår i: Clinical Transplantation. - : Wiley. - 0902-0063 .- 1399-0012. ; 27:6, s. E636-E643
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIt is well established that post-transplantation anemia (PTA) in renal transplant recipients (RTRs) is associated with reduced graft survival. However, there is an uncertainty of the effect of PTA on cardiovascular events and all-cause mortality. We examined prospectively in a large cohort of erythropoietin-naive patients the effects of PTA on cardiovascular morbidity, patient survival, and graft survival. MethodsA prospective cohort study of RTRs (n=2102) included in the ALERT study. Cox regression models were used to evaluate the impact of PTA on study endpoints: first occurrence of a major adverse cardiac event, all-cause death, and the incidence of death-censored graft loss. Mean follow-up was 6.7yr. All endpoints were adjudicated by an independent endpoint committee. ResultsTwenty-nine percent of women and 30% of men were anemic. Hemoglobin levels were not associated with any effect on cardiovascular morbidity and mortality (HR 0.97 [0.90-1.05] per g/dL, p=0.48) or all-cause death (HR 0.96 [0.90-1.03] per g/dL, p=0.24) after extensive multivariate adjustments for clinical and demographic factors. Hemoglobin levels were negatively associated with graft loss (HR 0.86 [0.80-0.92] per g/dL, p<0.001). ConclusionsPTA was not associated with an increased incidence of cardiovascular morbidity and mortality or all-cause mortality.
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