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Roberto Hernadez-Alejandro,
William Wall,
Anthony Jevnikar,
Patrick Luke,
Michael Sharpe,
David Russell,
Azeem Gangji, Edward Cole,
Sang Joseph Kim,
Marcus Selzner,
Shaf Keshavjee,
Dianne Hebert,
G V Ramesh Prasad,
Andrew Baker,
Greg Knoll,
Robyn Winterbottom,
Guiseppe Pagliarello,
Clare Payne,
Jeff Zaltzman
Canadian Anaesthetists? Society Journal 05/2012; 59(7):729. · 2.31 Impact Factor
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Roberto Hernadez-Alejandro,
William Wall,
Anthony Jevnikar,
Patrick Luke,
Michael Sharpe,
David Russell,
Azeem Gangji, Edward Cole,
Sang Joseph Kim,
Marcus Selzner,
Shaf Keshavjee,
Dianne Hebert,
G V Ramesh Prasad,
Andrew Baker,
Greg Knoll,
Robyn Winterbottom,
Guiseppe Pagliarello,
Clare Payne,
Jeff Zaltzman
[show abstract]
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ABSTRACT: The aim of this study was to explore donor and recipient outcomes from organ donation after cardiac death (DCD) in Ontario and to examine the impact of DCD on deceased donation rates in Ontario since its implementation.
Donor data were obtained from the Trillium Gift of Life Network (TGLN) TOTAL database from June 1, 2006 until May 31, 2009. All DCDs were tracked, including unsuccessful DCD attempts during that time. For the first 36 months after DCD implementation, all Ontario solid organ transplant programs that utilized organs from DCD provided clinical outcome data at one year. Total DCD activity until December 1, 2010 was also tracked. In addition, we compared organ donation and DCD rates across all Canadian jurisdictions and the USA.
For the first 36 months of DCD activity in Ontario, June 1, 2006 to May 31, 2009, there were 67 successful DCDs out of 87 attempted DCDs in 18 Ontario hospitals, resulting in 128 kidney, 41 liver, and 21 lung transplants. The one-year kidney patient and death-censored allograft survivals were 96 and 97%, respectively. Mean (SD) creatinine at 12 months was 150 (108) μmol·L(-1). In 26 (20%) extended criteria donors (ECD-DCD), the one-year creatinine was 206 (158) μmol·L(-1) vs 137 (80) μmol·L(-1) in 102 standard criteria donors (SCD-DCD) (P = 0.002). The one-year liver and lung allograft survivals were 78% and 70%, respectively. Since its implementation four and a half years ago, DCD has accounted for 10.9% of deceased donor activity in Ontario. In 2009, Ontario had a record number of organ donors. Of the 221 deceased donors, 37 (17%) donors were DCD. By December 1, 2010 there were 121 DCD Ontario donors resulting in > 300 solid organ transplants and accounting for 90% of all DCD activity in the country.
The rapid update of DCD in Ontario can be attributed to strong proponents in the critical care and transplantation communities with continued support from Trillium Gift of Life Network (TGLN). Ontario is the only province to demonstrate growth in deceased donor rates over the last decade (25% over the last four years), which can be attributed primarily to the success of its DCD activity.
Canadian Anaesthetists? Society Journal 07/2011; 58(7):599-605. · 2.31 Impact Factor
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Hallvard Holdaas,
Lionel Rostaing,
Daniel Serón, Edward Cole,
Jeremy Chapman,
Bengt Fellstrøm,
Erik H Strom,
Alan Jardine,
Karsten Midtvedt,
Uwe Machein,
Bettina Ulbricht,
Alexander Karpov,
Philip J O'Connell
[show abstract]
[hide abstract]
ABSTRACT: Benefits of conversion from calcineurin inhibitor (CNI) to mammalian target of rapamycin inhibitor-based immunosuppression in long-term kidney transplant patients remain uncertain.
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) 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.
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, 46.6±21.1 mL/min/1.73 m, and 46.0±20.4 mL/min/1.73 m in the CNI elimination, CNI minimization, and control groups, respectively. Differences between CNI elimination (1.12 mL/min/1.73 m, 95% confidence interval [CI] -3.51 to 5.76, P=0.63) and CNI minimization (0.59 mL/min/1.73 m, 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, 95% CI 2.1 to 20.8 mL/min/1.73 m, 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).
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.
Transplantation 06/2011; 92(4):410-8. · 4.00 Impact Factor
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Greg A Knoll,
Tom D Blydt-Hansen,
Patricia Campbell,
Marcelo Cantarovich, Edward Cole,
Todd Fairhead,
John S Gill,
Sita Gourishankar,
Diane Hebert,
Anthony Hodsman,
Andrew A House,
Atul Humar,
Martin Karpinski,
S Joseph Kim,
Rahul Mainra,
G V Ramesh Prasad
American Journal of Kidney Diseases 08/2010; 56(2):219-46. · 5.43 Impact Factor
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Sadollah Abedini,
Ingar Holme,
Winfried März,
Gisela Weihrauch,
Bengt Fellström,
Alan Jardine, Edward Cole,
Bart Maes,
Hans-Hellmut Neumayer,
Carola Grønhagen-Riska,
Patrice Ambühl,
Hallvard Holdaas
[show abstract]
[hide abstract]
ABSTRACT: Renal transplant recipients experience premature cardiovascular disease and death. The association of inflammation, all-cause mortality, and cardiovascular events in renal transplant recipients has not been examined in a large prospective controlled trial.
ALERT was a randomized, double-blind, placebo-controlled study of the effect of fluvastatin on cardiovascular and renal outcomes in 2102 renal transplant recipients. Patients initially randomized to fluvastatin or placebo in the 5- to 6-yr trial were offered open-label fluvastatin in a 2-yr extension to the original study. The association between inflammation markers, high-sensitivity C-reactive protein (hsCRP), and IL-6 on cardiovascular events and all-cause mortality was investigated.
The baseline IL-6 value was 2.9 +/- 1.9 pg/ml (n = 1751) and that of hsCRP was 3.8 +/- 6.7 mg/L (n = 1910). After adjustment for baseline values for established risk factors, the hazard ratios for a major cardiac event and all-cause mortality for IL-6 were 1.08 [95% confidence interval (CI), 1.01 to 1.15, P = 0.018] and 1.11 (95% CI, 1.05 to 1.18, P < 0.001), respectively. The adjusted hazard ratio for hsCRP for a cardiovascular event was 1.10 (95% CI, 1.01 to 1.20, P = 0.027) and for all-cause mortality was 1.15 (95% CI, 1.06 to 1.1.25, P = 0.049).
The inflammation markers IL-6 and hsCRP are independently associated with major cardiovascular events and all-cause mortality in renal transplant recipients.
Clinical Journal of the American Society of Nephrology 06/2009; 4(7):1246-54. · 5.23 Impact Factor
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[show abstract]
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ABSTRACT: 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.
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.
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).
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.
Arthritis & Rheumatism 05/2009; 60(4):1060-4. · 7.87 Impact Factor
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[show abstract]
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ABSTRACT: 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.
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.
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.
Risk factors for CBV events in renal transplant recipients differ according to subtype.
Transplantation 02/2009; 87(1):112-7. · 4.00 Impact Factor
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[show abstract]
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ABSTRACT: Steroids are effective immunosuppressants in renal transplantation but are associated with significant adverse effects. As a result, there has been increased interest in protocols utilizing steroid minimization. Initial trials stopped steroids at approximately 3 months, when the highest risk phase for acute rejection was over. As two randomized trials using cyclosporine and mycophenolate mofetil without induction therapy showed an unacceptably high acute rejection rate, more recent interest has focused on the cessation of steroids very early, usually within the first week after transplantation. Most protocols have used antibody induction combined with calcineurin inhibitors and mycophenolic acid derivatives. Uncontrolled studies have shown a low rate of acute rejection, but the most recent randomized controlled trials have demonstrated an increased risk of acute rejection. These trials have not shown any consistent difference in short-term patient or graft survival. Cardiovascular risk factors do not appear to be consistently improved by early steroid withdrawal. Most trials lack sufficient follow-up (5 years or more) to assess the impact of the increased acute rejection rate seen with early steroid withdrawal on long-term outcomes. Thus, the use of such protocols remains investigational.
Pediatric Nephrology 07/2008; 24(2):243-51. · 2.52 Impact Factor
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Canadian Medical Association Journal 03/2008; 178(5):568. · 8.22 Impact Factor
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Edward Cole
Drugs 02/2008; 68 Suppl 1:1-2. · 4.23 Impact Factor
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ABSTRACT: The calcineurin inhibitors (CNI) cyclosporine and tacrolimus remain the backbone of immunosuppression for most kidney transplant recipients. Despite many years of experience, protocols that optimize efficacy with minimal toxicity remain a subject of debate. Nevertheless, studies of the pharmacokinetic properties of the CNI, particularly cyclosporine, have led to improved dosing strategies. The purpose of this article is to review the current understanding of CNI pharmacokinetics and its relevance to proper dosing and monitoring of these medications. This article also reviews the trials that have helped to define the optimal dosages and discusses the effect of adjunctive immunosuppressive agents on CNI pharmacokinetics and dosing.
Clinical Journal of the American Society of Nephrology 04/2007; 2(2):374-84. · 5.23 Impact Factor
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Flavio Vincenti,
Amado de Andrés,
Thomas Becker,
Gabriel Choukroun, Edward Cole,
José M González-Posada,
Mysore A Kumar,
Richard Moore,
Silvio Nadalin,
Björn Nashan,
Lionel Rostaing,
Kazuhide Saito,
Norio Yoshimura
[show abstract]
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ABSTRACT: Addition of interleukin-2 receptor antagonist (IL-2RA) induction to calcineurin inhibitor (CNI)-based regimens reduces biopsy-proven acute rejection by 30-40%. IL-2RA induction facilitates early withdrawal of steroids, and supports the safe use of reduced-exposure CNI or delayed CNI introduction. IL-2RAs and rabbit antithymocyte globulin (Thymoglobulin) show comparable efficacy in patients at standard or low immunologic risk, but the adverse event profiles of lymphocyte-depleting agents are less favorable. IL-2RAs, uniquely, provide effective immunosuppression with similar tolerability to placebo.
Transplant International 07/2006; 19(6):446-57. · 2.92 Impact Factor
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[show abstract]
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ABSTRACT: Therapeutic drug monitoring for cyclosporine microemulsion (CsA-ME) is often performed using either trough levels (C0) or levels at 2 h post-dose (C2). This analysis assessed changes in C0 and C2 and their relationship to CsA-ME dose over time post-transplant in renal transplant patients.
Data were obtained from MO2ART, a prospective multicentre trial in which CsA-ME dose was adjusted based on C2 level. All 98 patients in whom C0 and C2 were available at day 5, month 3 and month 12 were included, out of 234 who completed the 12 month study. Normalized dose (ND) of CsA-ME, defined as dose per kilogram body weight, was calculated, together with C0/ND, C2/ND and C2/C0.
C0/ND and C2/ND both increased between day 5 and month 3: C0/ND from 33+/-15 to 53+/-24 (ng/ml)/(mg/kg) and C2/ND from 161+/-64 to 248+/-80 (ng/ml)/(mg/kg). Between month 3 and month 12, C2/ND remained stable but C0/ND decreased to 42+/-20 (ng/ml)/(mg/kg) while the C2/C0 ratio increased from 5.2+/-1.9 to 6.5+/-2.3, indicating an acceleration of drug elimination. The inter-individual coefficient of variation was higher for C0/ND than for C2/ND at 3 months (45 vs 32%, P<0.05) and at 12 months (48 vs 31%, P<0.01).
CsA clearance accelerates between months 3 and 12 post-transplant, resulting in lower C0 levels for a given exposure (as measured by C2). As a consequence, C0 monitoring may progressively underestimate CsA exposure during the first year post-transplant. C2 monitoring contributes to improved individualized CsA-ME treatment in both the de novo phase and beyond month 3.
Nephrology Dialysis Transplantation 01/2006; 21(1):197-202. · 3.40 Impact Factor
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Canadian Medical Association Journal 12/2005; 173(10):1181-4. · 8.22 Impact Factor
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Alan G Jardine,
Bengt Fellström,
John O Logan, Edward Cole,
Gudrun Nyberg,
Carola Grönhagen-Riska,
Søren Madsen,
Hans-Hellmut Neumayer,
Bart Maes,
Patrice Ambühl,
Anders G Olsson,
Terje Pedersen,
Hallvard Holdaas
[show abstract]
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ABSTRACT: 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.
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.
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).
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.
American Journal of Kidney Diseases 09/2005; 46(3):529-36. · 5.43 Impact Factor
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[show abstract]
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ABSTRACT: 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.
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.
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.
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.
Transplantation 06/2005; 79(9):1160-3. · 4.00 Impact Factor
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Hallvard Holdaas,
Bengt Fellström,
Alan G Jardine,
Gudrun Nyberg,
Carola Grönhagen-Riska,
Sören Madsen,
Hans-Hellmut Neumayer, Edward Cole,
Bart Maes,
Patrice Ambühl,
John O Logan,
Beatrix Staffler,
Claudio Gimpelewicz
[show abstract]
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ABSTRACT: 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.
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).
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).
Our data support an early introduction of fluvastatin therapy in a population of transplant recipients at high risk of premature coronary heart disease.
Nephrology Dialysis Transplantation 05/2005; 20(5):974-80. · 3.40 Impact Factor
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Sergio Stefoni,
Karsten Midtved, Edward Cole,
Eric Thervet,
Sandra Cockfield,
Matthias Buchler,
Lorenzo Toselli,
Luis M. Pallardo,
Francesco P. Schena,
Helen Pilmore,
Michèle Kessler,
Steve Chadban,
César Agost Carreño,
on behalf of the Study Group
[show abstract]
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ABSTRACT: Background. The clinical benefits of C2 monitoring of cyclosporine microemulsion have been demonstrated, but C2 targets in renal transplant recipients during the first year require validation.
Methods. MO2ART was a prospective, multicenter study of renal transplant recipients managed by C2 monitoring of cyclosporine microemulsion with steroids and mycophenolate mofetil or azathioprine. Patients were randomized on day 3 to two groups, which were managed from month 3 with higher or lower C2 target ranges (months 4-6, 1,000-1,200 ng/mL vs. 800-1,000 ng/mL; months 7-12, 800-1,000 ng/mL vs. 600-800 ng/mL, respectively). The primary endpoint was the glomerular filtration rate (GFR) at month 12.
Results. A total of 296 patients were recruited, of whom 250 remained in the study at 3 months (higher-C2, n=131; lower-C2, n=119). GFR at 12 months did not differ between the higher- and lower-C2 groups (65±17 mL/min vs. 66±14 mL/min). When patients were regrouped according to C2 achieved by months 8 to 12, those with the lowest C2 (<700 ng/mL) showed the lowest GFR at month 3 and the most pronounced increase in GFR between month 3 and month 12 (P=0.04). Five episodes of biopsy-proven acute rejection occurred after month 3 (higher-C2 group, n=2; lower-C2 group, n=3). The overall 12-month Kaplan-Meier incidence of biopsy-proven acute rejection was 13.7%. Patient and graft survival were 93% and 89%, respectively, at 12 months.
Conclusion. Both C2 target ranges investigated showed excellent and nearly equivalent outcomes at 12 months. The decision to target the higher or lower end of these C2 ranges should be made on an individual basis, taking into account patient and graft characteristics, and co-medication.
Transplantation 03/2005; 79(5):577-583. · 4.00 Impact Factor
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Sergio Stefoni,
Karsten Midtved, Edward Cole,
Eric Thervet,
Sandra Cockfield,
Matthias Buchler,
Lorenzo Toselli,
Luis M Pallardo,
Francesco P Schena,
Helen Pilmore,
Michèle Kessler,
Steve Chadban,
César Agost Carreño
[show abstract]
[hide abstract]
ABSTRACT: The clinical benefits of C2 monitoring of cyclosporine microemulsion have been demonstrated, but C2 targets in renal transplant recipients during the first year require validation.
MO2ART was a prospective, multicenter study of renal transplant recipients managed by C2 monitoring of cyclosporine microemulsion with steroids and mycophenolate mofetil or azathioprine. Patients were randomized on day 3 to two groups, which were managed from month 3 with higher or lower C2 target ranges (months 4-6, 1,000-1,200 ng/mL vs. 800-1,000 ng/mL; months 7-12, 800-1,000 ng/mL vs. 600-800 ng/mL, respectively). The primary endpoint was the glomerular filtration rate (GFR) at month 12.
A total of 296 patients were recruited, of whom 250 remained in the study at 3 months (higher-C2, n=131; lower-C2, n=119). GFR at 12 months did not differ between the higher- and lower-C2 groups (65+/-17 mL/min vs. 66+/-14 mL/min). When patients were regrouped according to C2 achieved by months 8 to 12, those with the lowest C2 (<700 ng/mL) showed the lowest GFR at month 3 and the most pronounced increase in GFR between month 3 and month 12 (P=0.04). Five episodes of biopsy-proven acute rejection occurred after month 3 (higher-C2 group, n=2; lower-C2 group, n=3). The overall 12-month Kaplan-Meier incidence of biopsy-proven acute rejection was 13.7%. Patient and graft survival were 93% and 89%, respectively, at 12 months.
Both C2 target ranges investigated showed excellent and nearly equivalent outcomes at 12 months. The decision to target the higher or lower end of these C2 ranges should be made on an individual basis, taking into account patient and graft characteristics, and co-medication.
Transplantation 03/2005; 79(5):577-83. · 4.00 Impact Factor
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Bengt Fellström,
Hallvard Holdaas,
Alan G Jardine,
Gudrun Nyberg,
Carola Grönhagen-Riska,
Søren Madsen,
Hans-Hellmut Neumayer, Edward Cole,
Bart Maes,
Patrice Ambühl,
Anders G Olsson,
Beatrix Staffler,
Terje R Pedersen
[show abstract]
[hide abstract]
ABSTRACT: The aim of the study was to identity risk factors for long-term renal transplant function and development of chronic allograft nephropathy (CAN) in renal transplant recipients included in the Assessment of Lescol in Renal Transplantation (ALERT) trial.
The ALERT trial was a randomized, double-blind, placebo-controlled study of the effect of fluvastatin, 40 and 80 mg/day, in renal transplant recipients who were randomized to receive fluvastatin (Lescol) (n = 1,050) or placebo (n = 1,052) over 5 to 6 years of follow-up. Renal endpoints including graft loss or doubling of serum creatinine or death were analyzed by univariate and multivariate regression analysis in the placebo group.
There were 137 graft losses (13.5%) in the placebo group, mainly caused by CAN (82%). Univariate risk factors for graft loss or doubling of serum creatinine were as follows: serum creatinine, proteinuria, hypertension, pulse pressure, time since transplantation, donor age, human leukocyte antigen-DR mismatches, treatment for rejection, low high-density lipoprotein cholesterol, and smoking. Multivariate analysis revealed independent risk factors for graft loss as follows: serum creatinine (relative risk [RR], 3.12 per 100-microM increase), proteinuria (RR, 1.64 per 1-g/24 hr increase), and pulse pressure (RR, 1.12 per 10 mm Hg), whereas age was a protective factor. With patient death in the composite endpoint, diabetes mellitus, smoking, age, and number of transplantations were also risk factors.
Independent risk factors for graft loss or doubling of serum creatinine or patient death are mainly related to renal transplant function, proteinuria, and blood pressure, which emphasizes the importance of renoprotective treatment regimens in this population.
Transplantation 02/2005; 79(2):205-12. · 4.00 Impact Factor
