Conversion From Twice-Daily Tacrolimus Capsules to Once-Daily Extended-Release Tacrolimus (LCPT): A Phase 2 Trial of Stable Renal Transplant Recipients

Transplantation - Current Issue Conversion From Twice-Daily Tacrolimus Capsules to Once-Daily Extended-Release Tacrolimus (LCPT): A Phase 2 Trial of Stable Renal Transplant Recipients

Background: LCP-Tacro is an extended-release formulation of tacrolimus designed for once-daily dosing. Phase 1 studies demonstrated greater bioavailability to twice-daily tacrolimus capsules and no new safety concerns. Methods: In this phase 2 study, adult stable kidney transplant patients on tacrolimus capsules (Prograf) twice-daily were converted to tacrolimus tablets (LCP-Tacro) once-daily; patients continued on LCP-Tacro once-daily for days 8 to 21; trough levels were to be maintained between 5 and 15 ng/mL; 24-hr pharmacokinetic assessments were done on days 7 (baseline pre-switch), 14, and 21. Results: Forty-seven patients completed LCP-Tacro dosing per protocol. The mean conversion ratio was 0.71. Pharmacokinetic data demonstrated consistent exposure (AUC) at the lower conversion dose. Cmax (P=0.0001), Cmax/Cmin ratio (P<0.001), percent fluctuation (P<0.0001), and swing (P=0.0004) were significantly lower and Tmax significantly (P<0.001) longer for LCP-Tacro versus Prograf. AUC24 and Cmin correlation coefficients after 7 and 14 days of therapy were 0.86 or more, demonstrating a robust correlation between LCP-Tacro tacrolimus exposure and trough levels. There were three serious adverse events; none were related to study drug and all were resolved. Conclusions: Stable kidney transplant patients can be safely converted from Prograf twice-daily to LCP-Tacro. The greater bioavailability of LCP-Tacro allows for once-daily dosing and similar (AUC) exposure at a dose approximately 30% less than the total daily dose of Prograf. LCP-Tacro displays flatter kinetics characterized by significantly lower peak-trough fluctuations.


http://journals.lww.com/transplantjournal/Fulltext/2013/07270/Conversion_From_Twice_Daily_Tacrolimus_Capsules_to.13.aspx

Cost-Effectiveness of Hand-Assisted Retroperitoneoscopic Versus Standard Laparoscopic Donor Nephrectomy: A Randomized Study

Transplantation - Current Issue Cost-Effectiveness of Hand-Assisted Retroperitoneoscopic Versus Standard Laparoscopic Donor Nephrectomy: A Randomized Study

Background: Live kidney donation has a clear economical benefit over dialysis and deceased-donor transplantation. Compared with mini-incision open donor nephrectomy, laparoscopic donor nephrectomy (LDN) is considered cost-effective. However, little is known on the cost-effectiveness of hand-assisted retroperitoneoscopic donor nephrectomy (HARP). This study evaluated the cost-effectiveness of HARP versus LDN. Methods: Alongside a randomized controlled trial, the cost-effectiveness of HARP versus LDN was assessed. Eighty-six donors were included in the LDN group and 82 in the HARP group. All in-hospital costs were recorded. During follow-up, return-to-work and other societal costs were documented up to 1 year. The EuroQol-5D questionnaire was administered up to 1 year postoperatively to calculate quality-adjusted life years (QALYs). Results: Mean total costs from a healthcare perspective were $8935 for HARP and $8650 for LDN (P=0.25). Mean total costs from a societal perspective were $16,357 for HARP and $16,286 for LDN (P=0.79). On average, donors completely resumed their daytime jobs on day 54 in the HARP group and on day 52 in the LDN group (P=0.65). LDN resulted in a gain of 0.005 QALYs. Conclusions: Absolute costs of both procedures are very low and the differences in costs and QALYs between LDN and HARP are very small. Other arguments, such as donor safety and pain, should determine the choice between HARP and LDN.


http://journals.lww.com/transplantjournal/Fulltext/2013/07270/Cost_Effectiveness_of_Hand_Assisted.10.aspx

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Low-Grade Proteinuria and Microalbuminuria in Renal Transplantation

Transplantation - Current Issue Low-Grade Proteinuria and Microalbuminuria in Renal Transplantation

Nephrotic-range proteinuria has been known for years to be associated with poor renal outcome. Newer evidence indicates that early (1–3 months after transplantation) low-grade proteinuria and microalbuminuria (1) provide information on the graft in terms of donor characteristics and ischemia/reperfusion injury, (2) may occur before the development of donor-specific antibodies, (3) predict the development of diabetes and cardiovascular events, and (4) are associated with reduced long-term graft and patient survivals. Low-grade proteinuria and microalbuminuria are also predictive of diabetes, cardiovascular morbidity, and death in nontransplanted populations, which may help us to understand the pathophysiology of low-grade proteinuria or microalbuminuria in renal transplantation. The impact of immunosuppressive medications, including mammalian target of rapamycin inhibitors, on graft survival is still discussed, and the effect on proteinuria is crucial to the debate. The fact that chronic allograft rejection may exist as early as 3 months after renal transplantation indicates that optimal management of low-grade proteinuria or microalbuminuria should occur very early after transplantation to improve long-term renal function and the overall outcome of renal transplant recipients. The presence of low-grade proteinuria or microalbuminuria early after transplantation must be taken into account to choose adequate immunosuppressive and antihypertensive medications. Limited information exists regarding the benefit of therapeutic interventions to reduce low-grade proteinuria or microalbuminuria. Whether renin angiotensin blockade results in optimal nephroprotection in patients with low-grade proteinuria or microalbuminuria is not proven, especially in the absence of chronic allograft nephropathy. Observational studies and randomized clinical trials yield conflicting results. Finally, randomized clinical trials are urgently needed.


http://journals.lww.com/transplantjournal/Fulltext/2013/07270/Low_Grade_Proteinuria_and_Microalbuminuria_in.4.aspx

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Immunogenicity of Quadrivalent Human Papillomavirus Vaccine in Organ Transplant Recipients.

AJT Immunogenicity of Quadrivalent Human Papillomavirus Vaccine in Organ Transplant Recipients.

• Kumar D, Unger ER, Panicker G, et al. 
• Immunogenicity of Quadrivalent Human Papillomavirus Vaccine in Organ Transplant Recipients. [JOURNAL ARTICLE]
• Am J Transplant 2013 Jul 9.

Solid organ transplant recipients are at risk of morbidity from human papillomavirus (HPV)-related diseases. Quadrivalent HPV vaccine is recommended for posttransplant patients but there are no data on vaccine immunogenicity. We determined the immunogenicity of HPV vaccine in a cohort of young adult transplant patients. Patients were immunized with three doses of quadrivalent HPV vaccine containing viral types 6, 11, 16 and 18. Immunogenicity was determined by type-specific viral-like protein ELISA. Four weeks after the last dose of vaccine, a vaccine response was seen in 63.2%, 68.4%, 63.2% and 52.6% for HPV 6, 11, 16 and 18, respectively. Factors that led to reduced immunogenicity were vaccination early after transplant (p = 0.019), having a lung transplant (p = 0.007) and having higher tacrolimus levels (p = 0.048). At 12 months, there were significant declines in antibody titer for all HPV types although the number of patients who remained seropositive did not significantly differ. The vaccine was safe and well tolerated. We show suboptimal immunogenicity of HPV vaccine in transplant patients. This is important for counseling patients who choose to receive this vaccine. Further studies are needed to determine an optimal HPV vaccine type and schedule for this population.

http://www.unboundmedicine.com/medline/citation/23837399/Immunogenicity_of_Quadrivalent_Human_Papillomavirus_Vaccine_in_Organ_Transplant_Recipients_

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Association Between Calcineurin Inhibitor Treatment and Peripheral Nerve Dysfunction in Renal Transplant Recipients.

AJT Association Between Calcineurin Inhibitor Treatment and Peripheral Nerve Dysfunction in Renal Transplant Recipients.

• Arnold R, Pussell BA, Pianta TJ, et al. 
• Association Between Calcineurin Inhibitor Treatment and Peripheral Nerve Dysfunction in Renal Transplant Recipients. [JOURNAL ARTICLE]
• Am J Transplant 2013 Jul 10.

Neurotoxicity is a significant clinical side effect of immunosuppressive treatment used in prophylaxis for rejection in solid organ transplants. This study aimed to provide insights into the mechanisms underlying neurotoxicity in patients receiving immunosuppressive treatment following renal transplantation. Clinical and neurophysiological assessments were undertaken in 38 patients receiving immunosuppression following renal transplantation, 19 receiving calcineurin inhibitor (CNI) therapy and 19 receiving a calcineurin-free (CNI-free) regimen. Groups were matched for age, gender, time since transplant and renal function and compared to normal controls (n = 20). The CNI group demonstrated marked differences in nerve excitability parameters, suggestive of nerve membrane depolarization (p < 0.05). Importantly, there were no differences between the two CNIs (cyclosporine A or tacrolimus). In contrast, CNI-free patients showed no differences to normal controls. The CNI-treated patients had a higher prevalence of clinical neuropathy and higher neuropathy severity scores. Longitudinal studies were undertaken in a cohort of subjects within 12 months of transplantation (n = 10). These studies demonstrated persistence of abnormalities in patients maintained on CNI-treatment and improvement noted in those who were switched to a CNI-free regimen. The results of this study have significant implications for selection, or continuation, of immunosuppressive therapy in renal transplant recipients, especially those with pre-existing neurological disability.

http://www.unboundmedicine.com/medline/citation/23841745/Association_Between_Calcineurin_Inhibitor_Treatment_and_Peripheral_Nerve_Dysfunction_in_Renal_Transplant_Recipients_

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Proteinuria and Outcome After Renal Transplantation: Ratios or Fractions?

Transplantation - Most Popular Articles Proteinuria and Outcome After Renal Transplantation: Ratios or Fractions?

Background: Proteinuria is associated with poorer outcomes in renal transplant recipients. Fractional excretion of total protein (FEPR) may better reflect kidney damage than urine protein-to-creatinine ratio (PCR). Methods: We assessed FEPR (FEPR = [serum creatinine × urine protein] / [serum protein × urine creatinine], %) and PCR ([urinary protein/urinary creatinine] × 1000, mg/mM) 1 year after first renal transplantation as predictors of transplant failure. The primary endpoints were transplant failure and death. The use of the tests was analyzed by constructing receiver operator characteristic curves and comparing the area under the curve. Using receiver operator characteristic analysis, patients were stratified into high- and low-risk groups. Results: Two hundred nineteen recipients were followed up for a median of 4.9 years. At a median of 2.7 years, 11.4% (n=25) of the transplants failed. Eight percent (n=17) of the patients died. The area under the curve was higher for FEPR than PCR (0.92 vs. 0.84). Patients with an FEPR of 0.019% or higher had a 3.4-fold (P=0.003) increased risk of transplant failure and a 2.3-fold (P=0.02) increased risk of death compared with those with an FEPR of less than 0.019%. Patients with a PCR of 97 mg/mM or greater had a 2.1-fold (P=0.04) increased risk of transplant failure and a 1.6-fold (P=0.04) increased risk of death compared with those with a PCR of less than 97 mg/mM (P=0.04). In multivariate analysis with time to transplant failure as the dependent variable, FEPR and PCR were independent predictors of transplant failure (hazards ratio, 1.07 [P=0.013] and 1.03 [P=0.03], respectively). Conclusions: FEPR and PCR at 1 year are independent predictors of transplant failure, but FEPR may be superior.


http://journals.lww.com/transplantjournal/Fulltext/2013/07150/Proteinuria_and_Outcome_After_Renal.12.aspx