Monday, February 13, 2012

Early conversion to a sirolimus-based, calcineurin-inhibitor-free immunosuppression in the SMART trial: observational results at 24 and 36 months after transplantation

Early conversion to a sirolimus-based, calcineurin-inhibitor-free immunosuppression in the SMART trial: observational results at 24 and 36 months after transplantation:

Summary

Early conversion to a calcineurin-inhibitor (CNI)-free maintenance immunosuppression with sirolimus (SRL), mycophenolate mofetil (MMF) and steroids was associated with an improved 1-year renal function as compared with a cyclosporine (CsA)-based regimen (SMART core-study). This observational follow-up describes 132 patients followed up within the SMART study framework for 36 months. At 36 months, renal function continued to be superior in SRL-treated patients [ITT-eGFR@36m: 60.88 vs. 53.72 (CsA) ml/min/1.73 m2, P = 0.031].

Correction of Postkidney Transplant Anemia Reduces Progression of Allograft Nephropathy

Correction of Postkidney Transplant Anemia Reduces Progression of Allograft Nephropathy:
Retrospective studies suggest that chronic allograft nephropathy might progress more rapidly in patients with post-transplant anemia, but whether correction of anemia improves renal outcomes is unknown. An open-label, multicenter, randomized controlled trial investigated the effect of epoetin-β to normalize hemoglobin values (13.0–15.0 g/dl, n=63) compared with partial correction of anemia (10.5–11.5 g/dl, n=62) on progression of nephropathy in transplant recipients with hemoglobin <11.5 g/dl and an estimated creatinine clearance (eCrCl) <50 ml/min per 1.73 m2.

Mycophenolate mofetil in low-risk renal transplantation in patients receiving no cyclosporine: a single-centre experience

Mycophenolate mofetil in low-risk renal transplantation in patients receiving no cyclosporine: a single-centre experience: Background.
We assess our long-term experience with regards the safety and efficacy of Mycophenolate Mofetil (MMF) in our low risk renal transplant population and compared it retrospectively to Azathioprine (AZA) immunosuppressive regimen.
Patients and methods.
Between January 1999 and December 2005, 240 renal transplants received MMF as part of their immunosuppressive protocol (MMF group). AZA group of 135 renal transplants was included for comparative analysis (AZA group). Patients received Cyclosporine was excluded from this study.

Very early steroid withdrawal or complete avoidance for kidney transplant recipients: a systematic review

Very early steroid withdrawal or complete avoidance for kidney transplant recipients: a systematic review: Background.
The safety and efficacy of early steroid withdrawal or avoidance in patients receiving a kidney transplant (KT) are controversial.
Methods.
We performed a systematic review and a meta-analysis of the randomized controlled studies about steroid avoidance or withdrawal after a few days in patients receiving a KT and treated with antibody induction and cyclosporine (CsA) or tacrolimus (Tac) plus mycophenolate mofetil (MMF) (nine available studies and 1934 participants).

Friday, February 3, 2012

A Randomized Controlled Trial of Intravenous or Oral Iron for Posttransplant Anemia in Kidney Transplantation

A Randomized Controlled Trial of Intravenous or Oral Iron for Posttransplant Anemia in Kidney Transplantation: Background: Anemia after kidney transplantation has been associated with poor transplant outcomes. We hypothesized that intravenous (IV) iron may more rapidly correct anemia than oral (PO) iron.
Methods: One hundred four kidney transplant recipients were prospectively randomized to IV iron polymaltose (500 mg single dose) or PO ferrous sulfate (210 mg elemental iron daily, continuously). The primary outcome was time to resolution of anemia, defined as hemoglobin more than or equal to 11 g/dL. Secondary outcomes included infections, blood transfusions, gastrointestinal side-effects, and acute rejection.

Thursday, February 2, 2012

A New Diagnostic Algorithm for Antibody-Mediated Microcirculation Inflammation in Kidney Transplants

A New Diagnostic Algorithm for Antibody-Mediated Microcirculation Inflammation in Kidney Transplants:
We studied the significance of microcirculation inflammation in kidney transplants, including 329 indication biopsies from 251 renal allograft recipients, who were mostly nonpresensitized (crossmatch negative). Glomerulitis (g) and peritubular capillaritis (ptc) were often associated with antibody-mediated rejection (65% and 75%, respectively), but were also found in other diseases in the absence of donor-specific antibody (DSA): T-cell-mediated rejection (ptc, g), glomerulonephritis (g) and acute tubular necrosis (ptc). To develop rules for reducing the nonspecificity of microcirculation inflammation and defining the best grading thresholds associated with DSA, we built and validated a decision tree to predict DSA.

Three-Year Outcomes From BENEFIT-EXT: A Phase III Study of Belatacept Versus Cyclosporine in Recipients of Extended Criteria Donor Kidneys

Three-Year Outcomes From BENEFIT-EXT: A Phase III Study of Belatacept Versus Cyclosporine in Recipients of Extended Criteria Donor Kidneys:
Recipients of extended-criteria donor (ECD) kidneys have poorer long-term outcomes compared to standard-criteria donor kidney recipients. We report 3-year outcomes from a randomized, phase III study in recipients of de novo ECD kidneys (n = 543) assigned (1:1:1) to either a more intensive (MI) or less intensive (LI) belatacept regimen, or cyclosporine. Three hundred twenty-three patients completed treatment by year 3. Patient survival with a functioning graft was comparable between groups (80% in MI, 82% in LI, 80% in cyclosporine).

The Once-Daily Formulation of Tacrolimus: A Step Forward in Kidney Transplantation?

The Once-Daily Formulation of Tacrolimus: A Step Forward in Kidney Transplantation?: Nonadherence is a critical issue in transplantation. Recently, Astellas designed a once-daily-extended release formulation of tacrolimus (Tac). Despite initial reports showing bioequivalence of Tac once-daily (Advagraf) with the original formulation requiring twice-daily intake (Tac twice-daily, Prograf), several groups have now shown a sustained decrease in Tac exposure upon conversion from Prograf to Advagraf. Here, we discuss the possible reasons for this observation and how it could affect the expected benefits of Advagraf, and we comment on the fact that a similar lack of bioequivalence might prevail with generic immunosuppressive drugs.

Generic Immunosuppression in Solid Organ Transplantation: A Canadian Perspective

Generic Immunosuppression in Solid Organ Transplantation: A Canadian Perspective: The introduction of generic immunosuppressant medications may present an opportunity for cost savings in solid organ transplantation if equivalent clinical outcomes to the branded counterparts can be achieved. An interprofessional working group of the Canadian Society of Transplantation was established to develop recommendations on the use of generic immunosuppression in solid organ transplant recipients (SOTR) based on a review of the available data. Under current Health Canada licensing requirements, a demonstration of bioequivalence with the branded formulation in healthy volunteers allows for bridging of clinical data.

Early Association of Low-Grade Albuminuria and Allograft Dysfunction Predicts Renal Transplant Outcomes

Early Association of Low-Grade Albuminuria and Allograft Dysfunction Predicts Renal Transplant Outcomes: Background: Data on the combined associations of albuminuria and estimated glomerular filtration rate (eGFR) with renal transplant outcomes are limited. Our objective was to explore how renal transplant outcomes could be predicted by a combined variable of early low-grade albuminuria and allograft dysfunction.
Methods: We studied a cohort of adult deceased-donor kidney transplant recipients who were subdivided into four groups according to median albuminuria (100 mg/day, interquartile range, 0-470 mg/day) and median eGFR (60 mL/min/1.73 m2; interquartile range, 30-73 mL/min/1.73 m2) at third month posttransplantation as follows: group I (albuminuria <100 and eGFR >60, n=238); group II (albuminuria >=100 and eGFR >60, n=151); group III (albuminuria <100 and eGFR <=60; n=167); and group IV (albuminuria >=100 and eGFR <=60, n=228).

Allosensitization Rate of Male Patients Awaiting First Kidney Grafts After Leuko-Depleted Blood Transfusion

Allosensitization Rate of Male Patients Awaiting First Kidney Grafts After Leuko-Depleted Blood Transfusion: Background: Blood transfusions are generally avoided for potential renal transplant recipients due to risk of human leukocyte antigen (HLA) allosensitization. Despite the near universal use of erythropoiesis-stimulating agents, there are still occasions when patients require blood transfusions for reasons such as resistance to erythropoiesis-stimulating agents or cardiovascular instability. The risk of allosensitization in renal patients is believed to be lower with leuko-depleted blood. We sought to quantify the risk of blood transfusion per se in male renal patients on the transplant waiting list for their first kidney graft, using sensitive solid phase antibody detection.

Wednesday, February 1, 2012

A Randomized Trial With Steroids and Antithymocyte Globulins Comparing Cyclosporine/Azathioprine Versus Tacrolimus/Mycophenolate Mofetil (CATM2) in Renal Transplantation

A Randomized Trial With Steroids and Antithymocyte Globulins Comparing Cyclosporine/Azathioprine Versus Tacrolimus/Mycophenolate Mofetil (CATM2) in Renal Transplantation: Background: The best immunosuppressive regimen in benefit-risk ratio in renal transplantation is debated. Nowadays, tacrolimus (Tac) and mycophenolate mofetil (MMF) are considered more efficient than cyclosporine A (CsA) and MMF, but recent studies have challenged this assumption.
Methods: We conducted a monocentric, prospective, open-labeled, randomized, and controlled trial comparing CsA/azathioprine (Aza) versus Tac/MMF in 289 kidney transplant recipients treated with antithymocyte globulins and prednisone. Primary outcome was the number of patients with clinically suspected acute rejection at 1 year. Secondary outcomes were the number of patients with biopsy-proven acute rejection (BPAR), estimated glomerular filtration rate (eGFR), patient and graft survivals, and adverse events at 1 and 3 years.

Everolimus as Primary Immunosuppression in Kidney Transplantation: Experience in Conversion From Calcineurin Inhibitors

Everolimus as Primary Immunosuppression in Kidney Transplantation: Experience in Conversion From Calcineurin Inhibitors: Background: We analyzed our clinical experience with everolimus (EVL) and identified prognostic factors for a successful conversion.
Methods: Retrospective study of 220 kidney recipients consecutively converted to EVL with calcineurin inhibitor elimination. We studied risk factors for proteinuria at 1 year after conversion, decline in renal function, and graft survival.
Results: Baseline creatinine clearance was 52.4+/-17.8 mL/min vs. 53.4+/-20.1 mL/min 1 year after conversion (P=0.150). Median proteinuria increased from 304 mg/day (interquartile range 160-507) to 458 mg/day (interquartile range 238-892; P<0.001).

Clinical Utility of Cytomegalovirus Cell-Mediated Immunity in Transplant Recipients With Cytomegalovirus Viremia

Clinical Utility of Cytomegalovirus Cell-Mediated Immunity in Transplant Recipients With Cytomegalovirus Viremia: Background. A CD8+ T-cell response to cytomegalovirus (CMV) has been associated with control of viral replication. Assessment shortly after the onset of asymptomatic viremia could help significantly refine preemptive strategies.
Methods. We conducted a prospective study of organ transplant recipients who developed asymptomatic low-level viremia not initially requiring antiviral therapy. Cell-mediated immunity (CMI) was measured shortly after viremia onset and longitudinally using the Quantiferon-CMV assay. The primary outcome was the ability to predict spontaneous clearance versus virologic and/or clinical progression.