Thursday, May 30, 2013

Sotrastaurin in Calcineurin Inhibitor-Free Regimen Using Everolimus in De Novo Kidney Transplant Recipients. [feedly]


 
 
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Sotrastaurin in Calcineurin Inhibitor-Free Regimen Using Everolimus in De Novo Kidney Transplant Recipients.
Sotrastaurin, a novel selective protein-kinase-C inhibitor, inhibits early T cell activation via a calcineurin-independent pathway. Efficacy and safety of sotrastaurin in a calcineurin inhibitor-free regimen were evaluated in this two-stage Phase II study of de novo kidney transplant recipients. Stage 1 randomized 131 patients (2:1) to sotrastaurin 300 mg or cyclosporine A (CsA). Stage 2 randomized 180 patients (1:1:1) to sotrastaurin 300 or 200 mg or CsA. All patients received basiliximab, everolimus (EVR) and prednisone. Primary endpoint was composite efficacy failure rate of treated biopsy-proven acute rejection, graft loss, death or lost to follow-up. Main safety assessment was estimated glomerular filtration rate (eGFR) by MDRD-4 at Month 12. Composite efficacy failure rates at 12 months were higher in sotrastaurin arms (Stage 1: 16.5% and 10.9% for sotrastaurin 300 mg and CsA; Stage 2: 27.2%, 34.5% and 19.4% for sotrastaurin 200 mg, 300 mg and CsA). eGFR was significantly better in sotrastaurin groups versus CsA at most time points, except at 12 months. Gastrointestinal and cardiac adverse events were more frequent with sotrastaurin. Higher treatment discontinuation, deaths and graft losses occurred with sotrastaurin 300 mg. Sotrastaurin combined with EVR showed higher efficacy failure rates and some improvement in renal allograft function compared to a CsA-based therapy.

Pretransplant Immediately Early-1-Specific T Cell Responses Provide Protection For CMV Infection After Kidney Transplantation. [feedly]


 
 
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Pretransplant Immediately Early-1-Specific T Cell Responses Provide Protection For CMV Infection After Kidney Transplantation.
Cytomegalovirus (CMV) infection is still a major complication after kidney transplantation. Although cytotoxic CMV-specific T cells play a crucial role controlling CMV survival and replication, current pretransplant risk assessment for CMV infection is only based on donor/recipient (IgG)-serostatus. Here, we evaluated the usefulness of monitoring pre- and 6-month CMV-specific T cell responses against two dominant CMV antigens (IE-1 and pp65) and a CMV lysate, using an IFN-γ Elispot, for predicting the advent of CMV infection in two cohorts of 137 kidney transplant recipients either receiving routine prophylaxis (n = 39) or preemptive treatment (n = 98). Incidence of CMV antigenemia/disease within the prophylaxis and preemptive group was 28%/20% and 22%/12%, respectively. Patients developing CMV infection showed significantly lower anti-IE-1-specific T cell responses than those that did not in both groups (p < 0.05). In a ROC curve analysis, low pretransplant anti-IE-1-specific T cell responses predicted the risk of both primary and late-onset CMV infection with high sensitivity and specificity (AUC > 0.70). Furthermore, when using most sensitive and specific Elispot cut-off values, a higher than 80% and 90% sensitivity and negative predictive value was obtained, respectively. Monitoring IE-1-specific T cell responses before transplantation may be useful for predicting posttransplant risk of CMV infection, thus potentially guiding decision-making regarding CMV preventive treatment.

Xenon Treatment Protects Against Cold Ischemia Associated Delayed Graft Function and Prolongs Graft Survival in Rats. [feedly]

Xenon Treatment Protects Against Cold Ischemia Associated Delayed Graft Function and Prolongs Graft Survival in Rats.
http://www.unboundmedicine.com/medline/citation/23710625/Xenon_Treatment_Protects_Against_Cold_Ischemia_Associated_Delayed_Graft_Function_and_Prolongs_Graft_Survival_in_Rats_?utm_source=feedly

Tuesday, May 28, 2013

Efficacy of Sotrastaurin Plus Tacrolimus After De Novo Kidney Transplantation: Randomized, Phase II Trial Results. [feedly]


 
 
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Efficacy of Sotrastaurin Plus Tacrolimus After De Novo Kidney Transplantation: Randomized, Phase II Trial Results.
Sotrastaurin, a novel immunosuppressant, blocks early T cell activation through protein kinase C inhibition. Efficacy and safety of sotrastaurin with tacrolimus were assessed in a dose-ranging non-inferiority study in renal transplant recipients. A total of 298 patients were randomized 1:1:1:1 to receive sotrastaurin 100 (n = 77; discontinued in December 2011) or 200 mg (n = 73) b.i.d. plus standard tacrolimus (sTAC; 5-12 ng/mL), sotrastaurin 300 mg (n = 75) b.i.d. plus reduced tacrolimus (rTAC; 2-5 ng/mL) or enteric-coated mycophenolic acid (MPA) plus sTAC (n = 73); all patients received basiliximab and corticosteroids. Composite efficacy failure (treated biopsy-proven acute rejection ≥ grade IA, graft loss, death or loss to follow up) rates at Month 12 were 18.8%, 12.4%, 10.9% and 14.0% for the sotrastaurin 100, 200 and 300 mg, and MPA groups, respectively. The median estimated glomerular filtration rates were 55.7, 53.3, 64.9 and 59.2 mL/min, respectively. Mean heart rates were faster with higher sotrastaurin doses and discontinuations due to adverse events and gastrointestinal adverse events were more common. Fewer patients in the sotrastaurin groups experienced leukopenia than in the MPA group (1.3-5.5% vs. 16.5%). Sotrastaurin 200 and 300 mg had comparable efficacy to MPA in prevention of rejection with no significant difference in renal function between the groups.

Thursday, May 16, 2013

Increased incidence of herpes zoster in the setting of cytomegalovirus preemptive therapy after kidney transplantation [feedly]


 
 
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Increased incidence of herpes zoster in the setting of cytomegalovirus preemptive therapy after kidney transplantation

Abstract

Background

Herpes zoster (HZ) is a common infectious disease after kidney transplantation (KT). The incidence of HZ may increase during cytomegalovirus (CMV) preemptive therapy. We therefore evaluated the incidence, risk factors, and clinical outcomes of HZ after KT, according to the type of CMV prophylaxis used.

Methods

We retrospectively established a cohort of KT recipients who underwent transplantation from June 2008 to May 2010. Patients were categorized into 3 groups according to CMV prophylaxis regimen: Group A (preemptive therapy), Group B (universal prophylaxis <3 months), and Group C (universal prophylaxis >3 months). The incidence rate of HZ was compared in each group, and risk factors for HZ were identified.

Results

The incidence rate of HZ was 46.6 (95% confidence interval [CI] 31.4–66.5) per 1000 person-years. The incidence rate was higher in Group A than in Group C (80.0 vs. 13.0 per 1000 person-years; P = 0.001). Median onset time of HZ after KT was shorter in Group A than in Group B (0.9 vs. 9.9 months; P < 0.001) and Group C (0.9 vs. 14.8 months; P = 0.008). Post-herpetic neuralgia occurred in 7 patients (23%). No visceral involvement or death was related to HZ. By multivariate analysis, only female gender (corrected relative risk 1.59; 95% CI 1.09–2.00) was independently associated with HZ development.

Conclusions

In the setting of CMV preemptive therapy, a differentiated varicella zoster virus-specific prophylaxis might be necessary for patients with HZ risk factors.


Tuesday, May 14, 2013

The long-term outcome of renal transplantation of IgA nephropathy and the impact of recurrence on graft survival [feedly]


 
 
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The long-term outcome of renal transplantation of IgA nephropathy and the impact of recurrence on graft survival
Background

Few data are available on allograft survival at 15 years, the impact and the predictors of recurrence of the original disease in renal transplanted patients with IgA nephropathy (IgAN). Methods

In this retrospective study, we compared the long-term outcome of renal transplant in 190 patients with IgAN with that of 380 non-diabetic controls and evaluated the impact of recurrence of IgAN on the graft outcome. Results

At 15 years, the patient survival was 88.3% in IgAN patients and 82.6% in controls (P = 0.12), while the death-censored graft survival was 62.6 and 72.4%, respectively (P = 0.038). IgAN had a higher cumulative incidence of graft failures in comparison with controls even considering death as a competing risk (P = 0.025). At multivariate analysis, IgAN [relative risk (RR) = 1.468, P = 0.026], delayed graft function recovery (RR = 2.394, P = 0.000) and acute rejection (RR = 2.51, P = 0.000) were predictive of graft loss. IgAN recurred in 42 grafts (22.1%), of them, 12 were lost for recurrence and in another 6 recurrence was considered a concomitant cause of graft loss. The 15-year death censored graft survival was 68.3% in non-recurrent and 51.2% in recurrent patients (P = 0.069). Pure graft survival of non-recurrent IgAN patients was similar to that of controls (P = 0.406). At Cox analysis, the recurrence of IgAN significantly reduced from 1981 to 2010 (P = 0.0065, RR = 0.936). Conclusions

IgAN emerged as an independent predictor of worse graft outcome in the long-term. Recurrence of IgAN seems to progressively reduce in transplants performed from 1981 to 2010.


Saturday, May 4, 2013

Plasma Cell Neoplasms in US Solid Organ Transplant Recipients. [feedly]


 
 
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Plasma Cell Neoplasms in US Solid Organ Transplant Recipients.
Transplant recipients have elevated risk for plasma cell neoplasms (PCNs, comprising multiple myeloma and plasmacytoma), but little is known about risk factors in the transplant setting. Through linkage of the US solid organ transplant registry with 15 state/regional cancer registries, we identified 140 PCNs in 202 600 recipients (1987-2009). PCN risk was 1.8-fold increased relative to the general population (standardized incidence ratio [SIR] 1.80, 95%CI 1.51-2.12). Among cases, 102 were multiple myeloma (SIR 1.41) and 38 were plasmacytoma (SIR 7.06). PCN incidence increased with age, but due to the rarity of PCNs in younger people in the general population, SIRs were highest in younger transplant recipients (p = 0.03). PCN risk was especially high in recipients who were Epstein-Barr virus (EBV) seronegative at transplantation (SIR 3.93). EBV status was known for 18 tumors, of which 7 (39%) were EBV positive. Following liver transplantation, PCN risk was higher in recipients with cholestatic liver disease (SIR 2.78); five of these cases had primary biliary cirrhosis (PBC). A role for primary EBV infection after transplantation is supported by the increased PCN risk in young EBV seronegative recipients and the presence of EBV in tumors. PBC may be another risk factor, perhaps by causing chronic immune activation.

Thursday, May 2, 2013

Literature Review of Passenger Lymphocyte Syndrome Following Renal Transplantation and Two Case Reports [feedly]


 
 
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Literature Review of Passenger Lymphocyte Syndrome Following Renal Transplantation and Two Case Reports

Abstract

Passenger lymphocyte syndrome (PLS) is an immune-mediated hemolysis. It occurs following ABO blood group mismatched solid organ and/or bone marrow transplantation between donor and recipient. We report two cases of PLS occurring after renal transplantation. Both recipients received live related kidney transplants; one from his mother and the other from his brother. The direction of blood group transfer, from donor to recipient, was O Rh D+ to A Rh D+ in both cases. Approximately 12 days after transplantation, both recipients showed a rapid fall in their hemoglobin levels with no identifiable bleeding source. DAT positive hemolysis was confirmed and anti-A antibodies were detected in recipient sera, confirming a diagnosis of PLS. Both cases required blood transfusion support to maintain their hemoglobin and both had good renal outcomes. We have identified 99 PLS cases following renal transplant in the English literature. Previous ABO sensitization, donor blood group O to recipient blood group A or B transfer, and ciclosporin treatment have been identified as risk factors for PLS. Clinical outcomes in general are good; nonetheless, cases of graft failure and deaths have been reported. Early diagnosis and appropriate treatment are important in at risk individuals.




Alberto Reino Buelvas
Médico Internista Nefrólogo
Hospital San Vicente de Paul
Grupo Trasplantes Renales
Director Médico Unidad Renal