Once-Daily Extended-Release Versus Twice-Daily Standard-Release Tacrolimus in Kidney Transplant Recipients: A Systematic Review [feedly]

 
 

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Once-Daily Extended-Release Versus Twice-Daily Standard-Release Tacrolimus in Kidney Transplant Recipients: A Systematic Review

Background: A simplified dosing regimen may improve drug compliance in kidney transplant recipients and long-term graft outcomes. We aimed to identify, appraise, and synthesize the current evidence comparing the relative safety and efficacy of the recently introduced daily versus standard twice-daily tacrolimus administration. Methods: We systematically reviewed all randomized controlled trials and observational studies that compared the outcomes of daily versus twice-daily tacrolimus formulation in kidney transplant recipients. Medline (from 1948 to July week 4 2011), Embase (1980 to 2011 week 31), the Cochrane Library (1991 to June 2011), and conference proceedings were searched without language restriction. Results: Six randomized controlled trials (n=2499) and 15 observational studies (n=2886) were included in the review. There were no significant differences in biopsy-proven acute rejection (two trials, n=1093; risk ratio [RR; confidence interval (CI)], 1.24 [0.93-1.65]; P=0.15; I2=0%), patient survival (three trials, n=1156; RR [CI], 0.99 [0.97-1.02]; P=0.55; I2=32%), and graft survival (three trials, n=1156; RR [CI], 0.99 [0.97-1.02]; P=0.67; I2=0%) between the two formulations at 12 months. Similar results for acute rejection (five studies, n=391; RR [CI], 0.99 [0.93-1.06]; P=0.84; I2=0%) and overall patient survival (two studies, n=218; RR [CI], 1.02 [0.94-1.10]; P=0.62; I2=0%) were observed in observational studies. Conclusions: Once-daily tacrolimus appears to be as effective as twice-daily tacrolimus up to 12 months after kidney transplantation. (C) 2013 Lippincott Williams & Wilkins, Inc.

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Intermediate-term outcome of single kidney grafts from pediatric donors weighing 10–14 kg in adult recipients [feedly]

 
 

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Intermediate-term outcome of single kidney grafts from pediatric donors weighing 10–14 kg in adult recipients

Abstract

Background

Kidneys from pediatric donors weighing <10 kg are preferably transplanted en bloc, while kidneys from donors weighing >15 kg can be safely transplanted as single kidneys. However, single kidney transplantation from donors weighing 10–14 kg is controversial and has not been well investigated.

Methods

We analyzed the outcome of 15 recipients of single kidneys from donors weighing 10–14 kg (study group) with 40 recipients receiving an allograft from ideal deceased donors (control group).

Results

After a follow-up of three yr, death-censored graft survival was 100% in both groups. The calculated creatinine clearance was lower in the study group at six months (53 vs. 71 mL/min; p = 0.01) and similar at 12 months (68 vs. 68 mL/min; p = 0.48), 24 months (81 vs. 70 mL/min; p = 0.58), and 36 months (74 vs. 69 mL/min; p = 0.59). Urinary albumin/creatinine ratios were comparable between the two groups up to two yr. At three yr, urinary albumin/creatinine ratios were higher in the study group than the control group (10.5 vs. 0.9 mg/mmol; p = 0.007). Surveillance biopsies at three and six months post-transplant revealed no evidence for focal segmental glomerulosclerosis in the study group.

Conclusions

Transplantation of single pediatric kidneys from donors weighing 10–14 kg into adult recipients provides excellent intermediate-term outcomes. Low-grade albuminuria, three yr post-transplant, might indicate late-onset hyperfiltration injury.

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Professor Henrik Ekberg (1951–2012): a life as a symphony [feedly]

 
 

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Professor Henrik Ekberg (1951–2012): a life as a symphony

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Monitoring for HHV-6 Infection After Renal Transplantation: Evaluation of Risk Factors for Sustained Viral Replication [feedly]

 
 

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Monitoring for HHV-6 Infection After Renal Transplantation: Evaluation of Risk Factors for Sustained Viral Replication

Background: Human herpesvirus-6 (HHV-6) is known to reactivate after renal transplantation and has been associated with several clinical manifestations. Risk factors for sustained viral replication, however, remain unclear. Methods: Thirty consecutive kidney transplant patients were prospectively followed for HHV-6 replication between February 2007 and February 2008. Plasma samples for DNA detection were collected from the donor and the recipient before transplantation and from the recipient weekly for the first 2 months after transplantation and then every 2 weeks for 2 additional months. HHV-6 active infection was defined as detection of viral DNA in plasma, by polymerase chain reaction, in at least two consecutive samples over an interval of at least 1 week. Results: Active viral infection was detected in 25% of the recipients before transplantation and 27% (8 of 30) of the patients after transplantation. The mean time to onset of viral replication was 28.1 days after transplantation and 7 of 8 (87.5%) were asymptomatic. Risk factors associated with active HHV-6 infection were receiving an organ from a living donor (P=0.028), recipients with IgM antibodies detected before transplantation (P=0.005), and pretransplantation recipient HHV-6 viral load more than 10,000 copies/mL plasma (P=0.034). Conclusions: Active HHV-6 infection occurs early after renal transplantation and is mostly asymptomatic. Donor or recipient infection may occur at the time of transplantation and are related to higher rates of posttransplantation infections.

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Effects of ACE Inhibitors on Long-Term Outcome of Renal Transplant Recipients: A Randomized Controlled Trial [feedly]

 
 

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Effects of ACE Inhibitors on Long-Term Outcome of Renal Transplant Recipients: A Randomized Controlled Trial

Background: Available data on the role of renin-angiotensin system blockade in renal transplantation are inconclusive. Herein, we report the long-term results of a randomized controlled trial planned to evaluate the impact of angiotensin-converting enzyme inhibitors (ACE-i) on the cardiovascular outcome of renal transplant recipients (RTRs) receiving calcineurin inhibitors, steroids, and mycophenolate mofetil. Methods: Thirty-six RTRs were allocated to receive ACE-i and 34 served as controls. Survival free of a composite endpoint consisting of death, major cardiovascular events, renal graft loss or creatinine doubling, and survival free of each single endpoint were analyzed in both groups according to a modified intention-to-treat analysis. Results: During a 10-year follow-up, three patients died (one in the ACE-i group and two controls) and three lost their graft (two receiving ACE-i and one control). Three major cardiovascular events were observed in the ACE-i group and 12 among controls (P=0.008). At the end of observation, a significant increase in urinary protein excretion rate was only observed in controls (P=0.017). Compared with controls, RTRs administered ACE-i had significantly better survival free of the combined endpoint (P=0.0102, log-rank test) and free of major cardiovascular events (P=0.0027) without significant differences in renal outcome. By Cox regression analysis, ACE-i therapy resulted in the most powerful predictor of survival free of composite endpoint (hazard ratio, 0.165; 95% confidence interval, 0.053–0.512; P=0.0018) and survival free of major cardiovascular events (hazard ratio, 0.209; 95% confidence interval, 0.068–0.636; P=0.0059). Conclusions: Prolonged therapy with ACE-i was associated with better general and cardiovascular outcome of RTRs without detrimental effects on renal graft function.

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Effect of Peripheral Vascular Disease on Kidney Allograft Outcomes: A Study of U.S. Renal Data System [feedly]

 
 

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Effect of Peripheral Vascular Disease on Kidney Allograft Outcomes: A Study of U.S. Renal Data System

Background: The U.S. Renal Data System was used to analyze renal allograft outcomes in patients with peripheral vascular disease (PVD) at the time of transplant listing. Methods: We used an incident cohort of patients who underwent renal transplantation between June 2004 and September 2009. We defined PVD as symptomatic PVD at wait-listing. Comorbid conditions were diabetes mellitus, ischemic heart disease, cerebrovascular disease, hypertension, and smoking. Chi-square test, Student's t test, and Cox regression were used for statistical associations. Results: The mean graft survival was 55.3±0.40 months in patients with PVD versus 60.8±0.06 months in patients without PVD. There was an increased risk of graft failure with PVD (hazard ratio, 2.01; 95% confidence interval, 1.83–2.21; P=0.0001). After adjusting for other variables, PVD remained an independent risk factor for graft failure. Patients with PVD had lower death-censored graft survival versus patients without PVD at 1 year (93.3% vs. 96.6%), 2 years (89.7% vs. 95%), and 3 years (87.2% vs. 93.7%). All-cause mortality was higher in PVD versus without PVD (6.2% vs. 3.0%). In African Americans, the mean allograft survival was 54.8±0.98, months with PVD versus 59.7±0.135 months without PVD (P=0.0001). In non–African Americans, the mean allograft survival was 55.4±0.44 months with PVD versus 61.1±0.069 months without PVD (P=0.0001). There were no differences in survival between African Americans with PVD and non–African Americans with PVD. Conclusions: Patients with PVD have inferior allograft and patient survival versus those without PVD. Caution should be exercised when placing patients with symptomatic PVD or amputation on the wait-list.

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Cancer risk with alemtuzumab following kidney transplantation [feedly]

 
 

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Cancer risk with alemtuzumab following kidney transplantation

Abstract

Alemtuzumab has been employed for induction therapy in kidney transplantation with low rates of acute rejection and excellent graft and patient survival. Antibody induction therapy has been linked to increased vulnerability to cancer. Data regarding malignancy rates with alemtuzumab are limited. We studied 1350 kidney transplant recipients (between 2001 and 2009) at the University of Pittsburgh Starzl Transplant Institute, for post-transplant de novo and recurrent malignancy, excluding non-melanoma skin cancer, among patients receiving alemtuzumab, thymoglobulin, and no induction therapies. Of the 1350 patients, 1002 (74.2%) received alemtuzumab, 205 (15.2%) received thymoglobulin, and 122 (9%) received no induction therapy. After excluding cancers occurring within 60 d post-transplantation, 43 (3.25%) malignancies were observed during a median follow-up time of 4.0 yr. The incidence of malignancy was 5.4% (1.09 per 100 patient-years [PY]) with thymoglobulin, 2.8% (0.74 per 100 PY) with alemtuzumab, and 3.3% (0.66 per 100 PY) with no induction (across all groups; p = 0.2342, thymoglobulin vs. alemtuzumab; p = 0.008). Thus, with the exception of non-melanoma skin cancer which we did not evaluate, alemtuzumab induction was not associated with increased cancer incidence post-kidney transplantation when compared to no induction therapy and was associated with lower cancer incidence when compared to thymoglobulin.

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Cancer risk with alemtuzumab following kidney transplantation

Cancer risk with alemtuzumab following kidney transplantation

Alemtuzumab has been employed for induction therapy in kidney transplantation with low rates of acute rejection and excellent graft and patient survival. Antibody induction therapy has been linked to increased vulnerability to cancer. Data regarding malignancy rates with alemtuzumab are limited. We studied 1350 kidney transplant recipients (between 2001 and 2009) at the University of Pittsburgh Starzl Transplant Institute, for post-transplant de novo and recurrent malignancy, excluding non-melanoma skin cancer, among patients receiving alemtuzumab, thymoglobulin, and no induction therapies. Of the 1350 patients, 1002 (74.2%) received alemtuzumab, 205 (15.2%) received thymoglobulin, and 122 (9%) received no induction therapy. After excluding cancers occurring within 60 d post-transplantation, 43 (3.25%) malignancies were observed during a median follow-up time of 4.0 yr. The incidence of malignancy was 5.4% (1.09 per 100 patient-years [PY]) with thymoglobulin, 2.8% (0.74 per 100 PY) with alemtuzumab, and 3.3% (0.66 per 100 PY) with no induction (across all groups; p = 0.2342, thymoglobulin vs. alemtuzumab; p = 0.008). Thus, with the exception of non-melanoma skin cancer which we did not evaluate, alemtuzumab induction was not associated with increased cancer incidence post-kidney transplantation when compared to no induction therapy and was associated with lower cancer incidence when compared to thymoglobulin.

Risks and Benefits of Preemptive Second Kidney Transplantation [feedly]

Risks and Benefits of Preemptive Second Kidney Transplantation

Background: Information to guide the timing of a second kidney transplantation is limited. Methods: We compared outcomes of 3509 preemptive and 14,075 nonpreemptive second kidney transplant recipients in the U.S. Renal Data System between 1995 and 2007. Results: Preemptive recipients had less acute rejection (12% vs. 16%; P<0.0001) and delayed graft function (8% vs. 23%; P<0.0001). Preemptive transplantation was associated with a lower multivariate adjusted risk of allograft failure from any cause including death (hazard ratio [HR], 0.88; 95% confidence interval [95% CI], 0.81–0.96) and death with a functioning graft (HR [95% CI], 0.76 [0.66–0.87]) but a similar risk of death-censored graft loss (HR [95% CI], 0.98 [0.88–1.08]). The benefits of preemptive transplantation were evident in all patients groups with first transplant survival equal to or more than 1 year; however, a 34% increased risk of death-censored graft loss was observed in preemptive recipients when first transplant survival was less than 1 year. Conclusions: Benefits and risks of preemptive transplantation vary between primary and second transplant recipients. Benefits in second transplant recipients are primarily due to decreased death with a functioning graft, with no difference in death-censored graft survival. Preemptive transplantation was beneficial when first transplant survival was equal to or more than 1 year but associated with increased risk when graft survival was less than 1 year.

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Class II Alloantibody and Mortality in Simultaneous Liver-Kidney Transplantation.

• O'Leary JG, Gebel HM, Ruiz R, et al. 
• Class II Alloantibody and Mortality in Simultaneous Liver-Kidney Transplantation. [JOURNAL ARTICLE]
• Am J Transplant 2013 Feb 22.
• AbstractPublisher Full Text

Hyperacute kidney rejection is unusual in crossmatch positive recipients of simultaneous liver-kidney transplants (SLKT). However, recent data suggest that these patients remain at risk for antibody-mediated kidney rejection. To further investigate the risk associated with donor-specific alloantibodies (DSA) in SLKT, we studied 86 consecutive SLKT patients with an available pre-SLKT serum sample. Serum samples were analyzed in a blinded fashion for HLA DSA using single antigen beads (median florescence intensity ≥ 2,000 = positive). Post-SLKT samples were analyzed when available (76%). Thirty patients had preformed DSA, and nine developed de novo DSA. Preformed class I DSA did not change the risk of rejection, patient or allograft survival. In contrast, preformed class II DSA was associated with a markedly increased risk of renal antibody mediated rejection (AMR) (p = 0.006), liver allograft rejection (p = 0.002), patient death (p = 0.02), liver allograft loss (p = 0.02) and renal allograft loss (p = 0.045). Multivariable modeling showed class II DSA (preformed or de novo) to be an independent predictor of patient death (HR = 2.2; p = 0.043) and liver allograft loss (HR = 2.2; p = 0.044). These data warrant reconsideration of the approach to DSA in SLKT.

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Página original: http://www.unboundmedicine.com/medline/citation/23433356/Class_II_Alloantibody_and_Mortality_in_Simultaneous_Liver_Kidney_Transplantation_

Chronic Kidney Disease After Liver Transplantation: Pretransplantation Risk Factors and Predictors During Follow-Up

Background: Chronic renal impairment is an emerging problem in the management of patients after liver transplantation (LT). Methods: We prospectively analyzed predictors of chronic kidney disease (CKD) after LT in 179 patients followed for a median of 63 months. Diagnosis of CKD was based on an estimated glomerular filtration rate (GFR) of less than 60 mL/min according to the current position statement from the Kidney Disease Improving Global Outcome. Pretransplantation risk factors were evaluated. A Cox regression analysis, with time-dependent variables evaluated during follow-up, was applied to realize a prognostic model for CKD, and a prognostic index was also calculated. The validity of the model was tested in 149 independent LT patients with a median follow-up of 46 months. Results: The cumulative incidence of CKD was 45% at 5 years after LT. Estimated GFR at LT was the only pretransplantation independent risk factor (beta, 0.33; standard error (beta), 0.07; 95% confidence interval, 0.95-0.98). Development of arterial hypertension (hazards ratio [HR], 1.83), episodes of severe infection (HR, 2.15), and estimated GFR (HR, 0.89) after LT were identified as independent prognostic factors at the Cox regression time-dependent analysis. The model was able to identify the patients at higher risk for the development of CKD in the validation set. Conclusions: Lower renal function at transplantation is associated with a higher risk of CKD after transplantation. A predictive model based on the variation of posttransplantation variables during the course of follow-up can help the clinicians to estimate the probability of CKD in the next 12 months. (C) 2013 Lippincott Williams & Wilkins, Inc.

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Página original: http://pdfs.journals.lww.com/transplantjournal/9000/00000/Chronic_Kidney_Disease_After_Liver.98648.pdf

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