Friday, May 18, 2012

Kidney Function and Risk of Cardiovascular Disease and Mortality in Kidney Transplant Recipients: The FAVORIT Trial

Kidney Function and Risk of Cardiovascular Disease and Mortality in Kidney Transplant Recipients: The FAVORIT Trial:
In kidney transplant recipients, cardiovascular disease (CVD) is the leading cause of death. The relationship of kidney function with CVD outcomes in transplant recipients remains uncertain. We performed a post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial to assess risk factors for CVD and mortality in kidney transplant recipients.

Friday, May 11, 2012

Successful outcome of ganciclovir-resistant cytomegalovirus infection in organ transplant recipients after conversion to mTOR inhibitors

Successful outcome of ganciclovir-resistant cytomegalovirus infection in organ transplant recipients after conversion to mTOR inhibitors:

Summary

Ganciclovir-resistant (GanR) cytomegalovirus (CMV) infection after organ transplantation is emerging as a significant therapeutic challenge. We report two cases of GanR CMV infection successfully managed by switching immunosuppression from calcineurin inhibitors to an mTOR inhibitor-based regimen. This salvage therapy should be considered when other options are not available.

Wednesday, May 9, 2012

Recurrent Dense Deposit Disease After Renal Transplantation: An Emerging Role for Complementary Therapies

Recurrent Dense Deposit Disease After Renal Transplantation: An Emerging Role for Complementary Therapies:
Dense deposit disease is a rare glomerulonephritis caused by uncontrolled stimulation of the alternative complement pathway. Allograft survival after kidney transplantation is significantly reduced by the high rate of disease recurrence. No therapeutic interventions have consistently improved outcomes for patients with primary or recurrent disease. This is the first reported case of recurrent dense deposit disease being managed with eculizumab. Within 4 weeks of renal transplantation, deteriorating graft function and increasing proteinuria were evident. A transplant biopsy confirmed the diagnosis of recurrent dense deposit disease. Eculizumab was considered after the failure of corticosteroid, rituximab and plasmapheresis to attenuate the rate of decline in allograft function. There was a marked clinical and biochemical response following the administration of eculizumab. This case provides the first evidence that eculizumab may have a place in the management of crescentic dense deposit disease. More information is necessary to clarify the effectiveness and role of eculizumab in dense deposit disease but the response in this patient was encouraging. The results of clinical trials of eculizumab in this condition are eagerly awaited.

Tuesday, May 8, 2012

Randomized Controlled Trial of Sirolimus for Renal Transplant Recipients at High Risk for Nonmelanoma Skin Cancer

Randomized Controlled Trial of Sirolimus for Renal Transplant Recipients at High Risk for Nonmelanoma Skin Cancer

Anemia After Kidney Transplantation; Its Prevalence, Risk Factors, and Independent Association With Graft and Patient Survival: A Time-Varying Analysis

Anemia After Kidney Transplantation; Its Prevalence, Risk Factors, and Independent Association With Graft and Patient Survival: A Time-Varying Analysis: Introduction: Posttransplant anemia and its association with transplant outcomes have not been properly studied.
Methods: We examined 530 renal allograft recipients transplanted at our center and followed up for 31.0±14.1 months. Hemoglobin (Hb), serum bicarbonate, and creatinine; use of erythropoiesis-stimulating agent (ESA) and iron; and immunosuppressive regimen data were obtained at multiple time points during 24-month posttransplant.
Results: The overall prevalence of anemia was 89.4% at the time of transplant, dropping to 49.2% at 1 year and 44.3% at 2 years. ESA use decreased from 25.6% at 1 month to 8.23% at 24 months, only in 30.9% to 51.2% with severe anemia; 21.0% to 29.2% received iron supplements. Factors independently predictive of Hb included male gender (β=0.64, P<0.001, confidence interval [CI]: 0.45–0.82), estimated glomerular filtration rate (β=0.21 per 10 mL/min/1.73 m2, P<0.001; CI: 0.16–0.27), bicarbonate (β=0.4 per 10 mmol/L increase, P<0.001; CI: 0.31–0.85), using angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (β=0.36, P<0.001; CI: 0.16–0.55), African American race (β=−0.34, P=0.001, CI:−0.54 to −0.14), iron (β=−0.28, P=0.003, CI:−0.47 to −0.09) and ESA use (β=−0.73, P<0.001, CI:−0.93 to −0.52), and prednisone (β=−0.46, P<0.001, CI:−0.71 to −0.22 for >10 mg/day vs. none). Using a competing-risk regression model, Hb less than 9 in men and less than 8 in women, was associated with 5.25-fold higher risk of death-censored graft loss compared with no anemia (adjusted, P=0.005, CI: 1.7–16.7). Degree of anemia also remained significantly associated with risk of death (hazard ratio [HR]: 2.2, P<0.1, CI: 0.9–5.6 for grade 2; HR: 3.9, P=0.009, CI: 1.4–10.8 for grade 3; and HR: 4.8, P=0.08, CI: 1.5–15.4 for grade 4, all vs. grade 0).
Conclusion: We showed that posttransplant anemia is common, and ESA/iron use remains suboptimal, and Hb is independently associated with graft failure and mortality.

Anti-Human Leukocyte Antigen Immunization After Early Allograft Nephrectomy

Anti-Human Leukocyte Antigen Immunization After Early Allograft Nephrectomy: Introduction: The occurrence of de novo anti-human leukocyte antigen (HLA) antibodies and donor-specific antibodies (DSAs) after early graft loss is not well known. The aims of this single-center study were to evaluate the incidence of de novo DSAs and non-DSA anti-HLA antibodies after allograft nephrectomy for early graft loss and to seek the predictive factors for the development of DSAs.
Materials and Methods: Thirty-two patients, who experienced an early graft loss (<3 months after transplantation) and required an allograft nephrectomy, and who were considered for retransplantation, were included in the study. Anti-HLA antibodies were assessed, using the Luminex assay, before transplantation, on day 15 and at months 1, 3, 6, and 9 after the nephrectomy, and then every 3 to 6 months until the last follow-up.
Results: The median time between transplantation and allograft nephrectomy was 2.5 (0–81) days. The median follow-up was 335 (30–1441) days. At month 9, postallograft nephrectomy, the incidence of DSAs was 56.6% (17/30). Anti-HLA class I and class II DSAs were detected, respectively, in 33.3% (10/30) and 30% (9/30) of patients. The incidence of de novo non-DSA anti-HLA antibodies was 64% (19/30): of these, 83.3% reacted to the donors’ epitopes. Induction therapy (type and dose) and the time between transplantation and allograft nephrectomy did not influence the incidence of DSAs. No independent predictive factor for the development of DSAs was identified.
Conclusion: Even after a short transplantation period, DSAs and non-DSA anti-HLA antibodies may develop in more than 50% of patients whose immunosuppression has been stopped after an allograft nephrectomy.

Eculizumab for Dense Deposit Disease and C3 Glomerulonephritis

Eculizumab for Dense Deposit Disease and C3 Glomerulonephritis: Background and objectives
The principle defect in dense deposit disease and C3 glomerulonephritis is hyperactivity of the alternative complement pathway. Eculizumab, a monoclonal antibody that binds to C5 to prevent formation of the membrane attack complex, may prove beneficial.

Design, setting, participants, & measurements
In this open-label, proof of concept efficacy and safety study, six subjects with dense deposit disease or C3 glomerulonephritis were treated with eculizumab every other week for 1 year. All had proteinuria >1 g/d and/or AKI at enrollment. Subjects underwent biopsy before enrollment and repeat biopsy at the 1-year mark.