Friday, September 30, 2011

Influenza Vaccination in the Organ Transplant Recipient: Review and Summary Recommendations†

Influenza Vaccination in the Organ Transplant Recipient: Review and Summary Recommendations†:
Influenza virus causes a spectrum of illness in transplant recipients with a high rate of lower respiratory disease. Seasonal influenza vaccination is an important public health measure recommended for transplant recipients and their close contacts. Vaccine has been shown to be safe and generally well tolerated in both adult and pediatric transplant recipients. However, responses to vaccine are variable and are dependent on various factors including time from transplantation and specific immunosuppressive medication. Seasonal influenza vaccine has demonstrated safety and no conclusive evidence exists for a link between vaccination and allograft dysfunction.

Do wound complications or lymphoceles occur more often in solid organ transplant recipients on mTOR inhibitors? A systematic review of randomized controlled trials

Do wound complications or lymphoceles occur more often in solid organ transplant recipients on mTOR inhibitors? A systematic review of randomized controlled trials:

Summary

mTOR inhibitors have been associated with wound complications and lymphoceles. We systematically reviewed randomized controlled trials (RCTs) to compare these outcomes for solid organ transplant recipients. Relevant medical databases were searched to identify RCTs in solid organ transplantation comparing mTOR inhibitors with an alternative therapy reporting on wound complications and/or lymphoceles. Methodological quality of RCTs was assessed. Pooled analyses were performed to calculate odds ratios (OR) and 95% confidence intervals (CI). Thirty-seven RCTs in kidney, heart, simultaneous pancreas-kidney and liver transplantation were included.

Effect of Smoking on Kidney Transplant Outcomes: Analysis of the United States Renal Data System

Effect of Smoking on Kidney Transplant Outcomes: Analysis of the United States Renal Data System: Background. We investigated the effect of smoking on postkidney transplant outcomes in the United States Renal Data System.
Methods. In a retrospective cohort of 41,705 adult Medicare primary renal transplant recipients in the United States Renal Data System database transplanted from January 1, 2000, to June 30, 2006, and followed through October 31, 2006, we assessed Medicare claims for smoking. The association between renal allograft loss and death and smoking as a time-dependent variable was assessed with Cox nonproportional hazards regression.

Kidney Transplantation With Minimized Maintenance: Alemtuzumab Induction With Tacrolimus Monotherapy—An Open Label, Randomized Trial

Kidney Transplantation With Minimized Maintenance: Alemtuzumab Induction With Tacrolimus Monotherapy—An Open Label, Randomized Trial: Background. Immunosuppressive regimens for kidney transplantation which reduce the long-term burden of immunosuppression are attractive, but little data are available to judge the safety and efficacy of the different strategies used. We tested the hypothesis that the simple, cheap, regimen of alemtuzumab induction combined with tacrolimus monotherapy maintenance provided equivalent outcomes to the more commonly used combination of interleukin-2 receptor monoclonal antibody induction with tacrolimus and mycophenolate mofetil combination maintenance, both regimens using steroid withdrawal after 7 days.

Results of a Prospective Randomized Trial of Sirolimus Conversion in Kidney Transplant Recipients on Early Corticosteroid Withdrawal

Results of a Prospective Randomized Trial of Sirolimus Conversion in Kidney Transplant Recipients on Early Corticosteroid Withdrawal: Background. The use of calcineurin inhibitors is associated with chronic nephrotoxicity and lower glomerular filtration rate (GFR). As a result, one strategy of transplant immunosuppression is calcineurin inhibitor elimination.
Methods. The aim of this study was to determine the outcome of a prospective randomized trial of kidney transplant recipients receiving rapid corticosteroid withdrawal, tacrolimus and mycophenolate mofetil (MMF) for 1 month followed by randomization to switch to sirolimus-MMF or to stay on tacrolimus-MMF. The primary outcome was the difference in measured GFR at 1 year using intention-to-treat analysis.

False-positive Aspergillus galactomannan assay in solid organ transplant recipients with histoplasmosis

False-positive Aspergillus galactomannan assay in solid organ transplant recipients with histoplasmosis:

Abstract:

Post-transplantation histoplasmosis may be acquired via inhalation, may result from endogenous reactivation, or may be derived from the allograft. The Histoplasma and Aspergillus enzyme-linked immunoassays are increasingly being relied upon for rapid diagnosis of fungal infections, especially in immunocompromised patients. We describe 4 cases of solid organ transplant recipients who had histoplasmosis and a falsely positive Aspergillus galactomannan (GM) obtained from the serum or bronchoalveolar lavage (BAL) fluid.

Detection of Polyomavirus BK Reactivation After Renal Transplantation Using an Intensive Decoy Cell Surveillance Program Is Cost-Effective

Detection of Polyomavirus BK Reactivation After Renal Transplantation Using an Intensive Decoy Cell Surveillance Program Is Cost-Effective: Background. Reactivation of polyomavirus BK (BKV) after renal transplantation can lead to allograft dysfunction or loss with early detection improving outcomes. Current guidelines recommend quantitative polymerase chain reaction for surveillance; however, urinary decoy cell detection is a potentially cost-effective alternative. We present the outcomes from an early intensive BKV surveillance program using decoy cell detection for initial screening starting 2 weeks after transplantation.
Methods. Records for all recipients of kidney (n=211) or simultaneous kidney and pancreas (n=102) transplants performed over 2 years in a single center were reviewed. Follow-up was for a minimum of 1 year. Urine cytology screening was performed fortnightly from 0 to 3 months after transplantation, monthly from 3 to 6 months then every 2 months from 6 to 12 months.

Pregnancy under everolimus-based immunosuppression

Pregnancy under everolimus-based immunosuppression:

Summary

The ability to give birth to a live child is one of the best success of kidney transplantation. While there are an increasing number of pregnancies reported in kidney transplant recipients treated with cyclosporine or tacrolimus, there is little evidence of pregnancy among kidney transplant recipients exposed to sirolimus or everolimus. We present the first successful delivery in an organ transplant recipient exposed to everolimus during the whole gestation. The absence of congenital anomalies in the child as well as the recipient’s successful renal outcome are promising, although pregnancy in renal transplant recipients exposed to everolimus should be considered at higher risk.

Immunosuppressant Regimen Based on Sirolimus Decreases Aortic Stiffness in Renal Transplant Recipients in Comparison to Cyclosporine.

Immunosuppressant Regimen Based on Sirolimus Decreases Aortic Stiffness in Renal Transplant Recipients in Comparison to Cyclosporine.: Joannidès R, Monteil C, de Ligny BH, et al.
Immunosuppressant Regimen Based on Sirolimus Decreases Aortic Stiffness in Renal Transplant Recipients in Comparison to Cyclosporine. [JOURNAL ARTICLE]
Am J Transplant 2011 Sep 19.


Whether or not a cyclosporine A (CsA)-free immunosuppressant regimen based on sirolimus (SRL) prevents aortic stiffening and improves central hemodynamics in renal recipients remains unknown. Forty-four patients (48 ± 2 years) enrolled in the CONCEPT trial were randomized at week 12 (W12) to continue CsA or switch to SRL, both associated with mycophenolate mofetil. Carotid systolic blood pressure (cSBP), pulse pressure (cPP), central pressure wave reflection (augmentation index, AIx) and carotid-to-femoral pulse-wave velocity (PWV: aortic stiffness) were blindly assessed at W12, W26 and W52 together with plasma endothelin-1 (ET-1), thiobarbituric acid-reactive substances (TBARS) and superoxide dismutase (SOD) and catalase erythrocyte activities. At W12, there was no difference between groups. At follow-up, PWV, cSBP, cPP and AIx were lower in the SRL group. The difference in PWV remained significant after adjustment for blood pressure and eGFR. In parallel, ET-1 decreased in the SRL group, while TBARS, SOD and catalase erythrocyte activities increased in both groups but to a lesser extent in the SRL group. Our results demonstrate that a CsA-free regimen based on SRL reduces aortic stiffness, plasma endothelin-1 and oxidative stress in renal recipients suggesting a protective effect on the arterial wall that may be translated into cardiovascular risk reduction.

Terminal Complement Inhibition Decreases Antibody-Mediated Rejection in Sensitized Renal Transplant Recipients

Terminal Complement Inhibition Decreases Antibody-Mediated Rejection in Sensitized Renal Transplant Recipients:
Sensitized renal transplant recipients with high levels of donor-specific alloantibody (DSA) commonly develop antibody-mediated rejection (AMR), which may cause acute graft loss or shorten allograft survival. We examined the efficacy of terminal complement inhibition with the humanized anti-C5 antibody, eculizumab, in the prevention AMR in renal transplant recipients with a positive crossmatch against their living donor.

The PROMISE Study: A Phase 2b Multicenter Study of Voclosporin (ISA247) Versus Tacrolimus in De Novo Kidney Transplantation

The PROMISE Study: A Phase 2b Multicenter Study of Voclosporin (ISA247) Versus Tacrolimus in De Novo Kidney Transplantation:
Voclosporin (VCS, ISA247) is a novel calcineurin inhibitor being developed for organ transplantation. PROMISE was a 6-month, multicenter, randomized, open-label study of three ascending concentration-controlled groups of VCS (low, medium and high) compared to tacrolimus (TAC) in 334 low-risk renal transplant recipients. The primary endpoint was demonstration of noninferiority of biopsy proven acute rejection (BPAR) rates.

Wednesday, September 21, 2011

Living Donor Kidney Transplantation: The Effects of Donor Age and Gender on Short- and Long-Term Outcomes

Living Donor Kidney Transplantation: The Effects of Donor Age and Gender on Short- and Long-Term Outcomes: Background. The influence of donor age and sex on acute rejection episodes and short- and long-term graft survival in living donor (LD) kidney transplantation has not been well characterized.
Methods. This prospective cohort study includes 739 first time LD transplantations with median follow-up time of 55.1 months. Death censored graft survival according to donor age and sex was compared with Kaplan-Meier plots. Cox regression was performed to estimate the association between different risk factors and graft survival and acute rejection episodes.

New Computerized Color Image Analysis for the Quantification of Interstitial Fibrosis in Renal Transplantation

New Computerized Color Image Analysis for the Quantification of Interstitial Fibrosis in Renal Transplantation: Background. Chronic allograft injury, the primary cause of late allograft failure in renal transplantation, can be diagnosed early at a preclinical stage by histopathological changes such as interstitial fibrosis (IF). Currently, assessed by semiquantitative analysis in the Banff classification, IF quantification is limited by pathologist's subjective interpretation.

Management of Primary Symptomatic Lymphocele After Kidney Transplantation: A Systematic Review

Management of Primary Symptomatic Lymphocele After Kidney Transplantation: A Systematic Review: Background. Management of lymphoceles after kidney transplantation is highly variable. The aim of this study was to evaluate and compare the different approaches of lymphocele management among kidney transplant recipients.
Methods. MEDLINE and EMBASE were systematically searched for case studies published between 1954 and 2010. Inclusion criteria were symptomatic lymphoceles developing in recipients of deceased or living donor kidneys with specified intervention and outcome. Primary outcome was the rate of recurrence. Secondary outcomes were the rate of conversion from laparoscopic to open surgery, hospital stay, and complication rates.

Posttransplant Donor-Specific Anti-HLA Antibodies Negatively Impact Pancreas Transplantation Outcome

Posttransplant Donor-Specific Anti-HLA Antibodies Negatively Impact Pancreas Transplantation Outcome:
During a 9-year follow-up, 167 consecutive pancreas transplant recipients (152 simultaneous pancreas-kidney [SPK]) were followed for the detection of posttransplant anti-HLA antibodies. Forty patients (24%) developed anti-HLA antibodies, 26 (65%) had donor-specific antibodies (DSA; 61% anticlass 2) and 14 (35%) non-DSA (78.6% anticlass 1).

Friday, September 9, 2011

Randomized Trial of Immunosuppressive Regimens in Renal Transplantation

Randomized Trial of Immunosuppressive Regimens in Renal Transplantation:
The optimal long-term regimen for immunosuppression for kidney transplant recipients is unknown. We conducted a randomized trial involving 150 kidney transplant recipients to compare tacrolimus/sirolimus, tacrolimus/mycophenolate mofetil (MMF), and cyclosporine/sirolimus. All patients received daclizumab induction and maintenance corticosteroids. Median follow-up was 8 yr post-transplant.

Trends in the Timing of Pre-emptive Kidney Transplantation

Trends in the Timing of Pre-emptive Kidney Transplantation:
Pre-emptive kidney transplantation is considered the best available renal replacement therapy, but no guidelines exist to direct its timing during CKD progression. We used a national cohort of 19,471 first-time pre-emptive kidney transplant recipients between 1995–2009 to evaluate patterns and implications of transplant timing. Mean estimated GFR (eGFR) at the time of pre-emptive transplant increased significantly over time, from 9.2 ml/min/1.73m2 in 1995 to 13.8 ml/min/1.73m2 in 2009 (P<0.001).

Clinical Utility of Molecular Surveillance for Cytomegalovirus After Antiviral Prophylaxis in High-Risk Solid Organ Transplant Recipients

Clinical Utility of Molecular Surveillance for Cytomegalovirus After Antiviral Prophylaxis in High-Risk Solid Organ Transplant Recipients: Background. Cytomegalovirus (CMV) disease after discontinuation of prophylaxis is a significant problem for CMV-seronegative recipients of CMV-seropositive organs (donor seropositive and recipient seronegative [D+/R-]). Virologic monitoring after prophylaxis has been proposed as a way to prevent late-onset disease.
Methods. We reviewed the efficacy of this strategy. CMV D+/R- organ transplant recipients received 3 to 6 months of antiviral prophylaxis, and then viral loads were performed weekly for 8 weeks. Preemptive antiviral therapy was initiated at a predefined threshold.

Systematic Review: Kidney Transplantation Compared With Dialysis in Clinically Relevant Outcomes

Systematic Review: Kidney Transplantation Compared With Dialysis in Clinically Relevant Outcomes:
Individual studies indicate that kidney transplantation is associated with lower mortality and improved quality of life compared with chronic dialysis treatment. We did a systematic review to summarize the benefits of transplantation, aiming to identify characteristics associated with especially large or small relative benefit. Results were not pooled because of expected diversity inherent to observational studies. Risk of bias was assessed using the Downs and Black checklist and items related to time-to-event analysis techniques.

Specificity of Histological Markers of Long-Term CNI Nephrotoxicity in Kidney-Transplant Recipients Under Low-Dose Cyclosporine Therapy

Specificity of Histological Markers of Long-Term CNI Nephrotoxicity in Kidney-Transplant Recipients Under Low-Dose Cyclosporine Therapy:
The specificity of chronic histological lesions induced by calcineurin inhibitors (CNI) is often questioned, but few studies have directly compared long-term lesions in renal-transplant patients who received this treatment and those who did not. We therefore conducted a retrospective study of 141 kidney-transplant recipients treated with (n = 48) or without (n = 93) cyclosporine (CsA) to compare the histological lesions observed at 3-month, 24-month and 10-year protocol biopsies. All of the chronic elementary lesions (glomerulosclerosis, interstitial fibrosis, tubular atrophy, arteriolar hyalinosis, fibrointimal thickening) progressed in frequency and severity in both groups, although significantly more in the CsA group.

Bilateral Native Ureteral Ligation Without Nephrectomy in the Management of Kidney Transplant Recipients With Native Proteinuria

Bilateral Native Ureteral Ligation Without Nephrectomy in the Management of Kidney Transplant Recipients With Native Proteinuria:
The aim of this study was to assess the safety of bilateral native ureteral ligation (BNUL) without nephrectomy in the management of native proteinuria in kidney transplant (KTx) recipients. We retrospectively studied 17 patients who underwent BNUL between 2002 and 2010 with a median preoperative 24 h protein concentration of 2140 (range 1020–25 000) mg/L. Fifteen of the 17 patients had focal segmental glomerulosclerosis as their primary renal disease and ligation was employed to facilitate the diagnosis of early recurrence. The BNUL was performed simultaneously with KTx in 14 patients. Surgical techniques were: open (n = 5), pure laparoscopic (n = 1) and a hybrid of hand-assisted laparoscopic surgical/open approach (n = 12) used at the time of transplantation via the transplant incision. At a median follow-up of 46 months (range 1–59), no patient had a complication related to BNUL and none required interventions associated with their native kidneys. BNUL without nephrectomy seems to be a safe technique to manage native proteinuria in renal transplant candidates.

Validation of Urinary CXCL10 As a Marker of Borderline, Subclinical, and Clinical Tubulitis

Validation of Urinary CXCL10 As a Marker of Borderline, Subclinical, and Clinical Tubulitis: Background. Renal allograft injury secondary to subclinical and clinical tubulitis remains an important cause of allograft fibrosis and loss despite modern immunosuppression. The goal of this study was to validate the previously reported use of urinary CXCL10 (interferon-[gamma]-induced protein of 10 kDa) as a noninvasive marker of tubulitis in an independent clinical cohort.
Methods. Urine samples (n=102) from 91 patients with protocol or indication biopsies were assayed for urinary CXCL10 using ELISA. The groups analyzed were as follows: normal histology (n=22); interstitial fibrosis and tubular atrophy (IFTA) (n=20); IFTA and borderline tubulitis (n=13); borderline (n=13), subclinical (n=17); and clinical tubulitis (n=17) without IFTA.

Use of the QuantiFERON-TB Gold interferon-gamma release assay for screening transplant candidates: a single-center retrospective study

Use of the QuantiFERON-TB Gold interferon-gamma release assay for screening transplant candidates: a single-center retrospective study:
N. Theodoropoulos, F. Lanternier, J. Rassiwala, G. McNatt, L. Preczewski, E. DeMayo, V. Stosor, M.G. Ison. Use of the QuantiFERON-TB Gold interferon-gamma release assay for screening transplant candidates: a single-center retrospective study. Transpl Infect Dis 2011. All rights reserved
Background. Tuberculosis (TB) reactivation is a rare but significant complication of organ transplantation, and screening of all transplant candidates for latent infection is recommended with either an interferon-γ release assay (IGRA) or tuberculin skin test (TST).

Single shot of alemtuzumab as induction therapy after kidney transplantation is sufficient

Single shot of alemtuzumab as induction therapy after kidney transplantation is sufficient:

Summary

In an earlier study, we were able to show that Tac monotherapy following 2 × 20 mg alemtuzumab induction is at least as effective as Tac-based triple-drug immunosuppression in cadaveric renal transplantation. We were interested to learn whether 1 × 30 mg of alemtuzumab is as effective as 2 × 20 mg. Patients of the initial study group (group A) received 20 mg alemtuzumab on days 0 and 2, and tac monotherapy from day 2 on. This group acted as control group for the new arm (group C), where patients were given only 1 × 30 mg alemtuzumab on day 0 followed by Tac monotherapy from day 2 on with the same target levels as in the control group. Frequency of rejection at 6 months was 15% in the control group compared to 6% in the study group and 20% at 12 months in group A versus 6% in group C (P = 0.034). Time to rejection was 4.9 months in group A and 0.8 in group C. One-year patient survival was 98.5% in both groups, graft survival 96.9% in group A, and 98.5% in group C. Safety profile was similar in both groups apart from more viral and bacterial infections in group C. Single shot alemtuzumab induction of 30 mg is as effective as 2 × 20 mg in cadaveric renal transplantation.