Wednesday, December 28, 2011

Association of Immunosuppressive Maintenance Regimens With Posttransplant Lymphoproliferative Disorder in Kidney Transplant Recipients

Association of Immunosuppressive Maintenance Regimens With Posttransplant Lymphoproliferative Disorder in Kidney Transplant Recipients: Background. The association of immunosuppressive regimens (ISRs) with posttransplant lymphoproliferative disorder (PTLD) may be related with the Epstein-Barr virus (EBV) recipient serostatus.
Methods. We selected primary kidney transplant recipients from Organ Procurement Transplant Network/United Network for Organ Sharing database (2000–2009) who were discharged with a functioning graft and were receiving an ISR including an antiproliferative drug and a calcineurin inhibitor as follows: mycophenolate mofetil (MMF)/mycophenolate sodium+tacrolimus (TAC), MMF+cyclosporine A (CsA); mammalian target of rapamycin inhibitor (mTORi)+TAC; and mTORi+CsA. Adjusted risks of PTLD, rejection, death, and graft failure were examined in all recipients and compared between EBV+ and EBV− recipients.

Impact of Early Conversion From Tacrolimus to Sirolimus on Chronic Allograft Changes in Kidney Recipients on Rapid Steroid Withdrawal

Impact of Early Conversion From Tacrolimus to Sirolimus on Chronic Allograft Changes in Kidney Recipients on Rapid Steroid Withdrawal: Background. Calcineurin-inhibitor therapy is a contributing factor to the origin of interstitial fibrosis and tubular atrophy (IFTA).
Methods. We conducted a prospective randomized trial of conversion of tacrolimus to sirolimus at 1-month posttransplant in kidney transplant recipients on rapid steroid withdrawal. We compared the chronic changes (IFTA and sum of Banff chronic scores—Total Score) on protocol biopsies at 1 month, 1 year, and 2 years in all randomized patients. We compared the outcomes between treatment groups and analyzed the impact of previous rejection on the chronic changes.

Early Subclinical Rejection as a Risk Factor for Late Chronic Humoral Rejection

Early Subclinical Rejection as a Risk Factor for Late Chronic Humoral Rejection: Background. Subclinical rejection and interstitial fibrosis and tubular atrophy (IF/TA) in protocol biopsies are associated with outcome. We study the relationship between histologic lesions in early protocol biopsies and histologic diagnoses in late biopsies for cause.
Materials and Methods. Renal transplants with a protocol biopsy performed within the first 6 months posttransplant between 1988 and 2006 were reviewed. Biopsies were evaluated according to Banff criteria, and C4d staining was available in biopsies for cause.
Results. Of the 517 renal transplants with a protocol biopsy, 109 had a subsequent biopsy for cause which showed the following histological diagnoses: chronic humoral rejection (CHR) (n=44), IF/TA (n=42), recurrence of the primary disease (n=11), de novo glomerulonephritis (n=7), T-cell-mediated rejection (n=4), and polyoma virus nephropathy (n=1). The proportion of retransplants (15.9% vs. 2.3%, P=0.058) and the prevalence of subclinical rejection were higher in patients with CHR than in patients with IF/TA (52.3% vs. 28.6%, P=0.0253). Demographic donor and recipient characteristics and clinical data at the time of protocol biopsy were not different between groups. Logistic regression analysis showed that subclinical rejection (relative risk, 2.52; 95% confidence interval, 1.1–6.3; P=0.047) but not retransplantation (relative risk, 6.7; 95% confidence interval, 0.8–58.8; P=0.085) was associated with CHR.
Conclusion. Subclinical rejection in early protocol biopsies is associated with late appearance of CHR.

Monday, December 26, 2011

Reduced Fracture Risk With Early Corticosteroid Withdrawal After Kidney Transplant

Reduced Fracture Risk With Early Corticosteroid Withdrawal After Kidney Transplant:
Corticosteroid use after kidney transplantation results in severe bone loss and high fracture risk. Although corticosteroid withdrawal in the early posttransplant period has been associated with bone mass preservation, there are no published data regarding corticosteroid withdrawal and risk of fracture. We hypothesized lower fracture incidence in patients discharged from the hospital without than with corticosteroids after transplantation. From the United States Renal Data System (USRDS), 77 430 patients were identified who received their first kidney transplant from 2000 to 2006. Fracture incidence leading to hospitalization was determined from 2000 to 2007; discharge immunosuppression was determined from United Networks for Organ Sharing forms. Time-to-event analyses were used to evaluate fracture risk. Median (interquartile range) follow-up was 1448 (808–2061) days. There were 2395 fractures during follow-up; fracture incidence rates were 0.008 and 0.0058 per patient-year for recipients discharged with and without corticosteroid, respectively. Corticosteroid withdrawal was associated with a 31% fracture risk reduction (HR 0.69; 95% CI 0.59–0.81). Fractures associated with hospitalization are significantly lower with regimens that withdraw corticosteroid. As this study likely underestimates overall fracture incidence, prospective studies are needed to determine differences in overall fracture risk in patients managed with and without corticosteroids after kidney transplantation.

Valganciclovir Prophylaxis Versus Preemptive Therapy in Cytomegalovirus-Positive Renal Allograft Recipients: 1-Year Results of a Randomized Clinical Trial

Valganciclovir Prophylaxis Versus Preemptive Therapy in Cytomegalovirus-Positive Renal Allograft Recipients: 1-Year Results of a Randomized Clinical Trial: Background. Cytomegalovirus (CMV) prevention can be achieved by prophylaxis or preemptive therapy. We performed a prospective randomized trial to determine whether renal transplant recipients with a positive CMV serostatus (R+) had a higher rate of CMV infection and disease after transplantation when treated preemptively for CMV infection, compared with primary valganciclovir prophylaxis.
Methods. Prophylaxis was 2×450 mg oral valganciclovir/day for 100 days; preemptive patients were monitored by CMV-polymerase chain reaction (PCR), and after a positive PCR test received 2×900 mg valganciclovir/day for at least 14 days followed by secondary prophylaxis. Valganciclovir dosage was adjusted according to renal function. Patients are followed up for 5 years and initial 12-month data are presented. Two hundred and ninety-six recipients were analyzed (168 donor/recipient seropositive [D+/R+], 128 donor seronegative/recipient seropositive [D−/R+]; 146 receiving prophylaxis and 150 preemptive therapy).
Results. Overall, CMV infection (asymptomatic CMV viral load ≥400 CMV DNA copies/mL proven by CMV-PCR) was significantly higher in recipients under preemptive therapy (38.7% vs. 11.0%, P<0.0001), with the highest incidence in D+/R+ preemptive patients (53.8% vs. 15.6%, P<0.0001). D+/R+ recipients with preemptive therapy also had the highest rate of CMV disease (CMV syndrome and tissue-invasive disease that was clinically diagnosed and biopsy proven) (19.2% vs. 4.4%, P=0.003). Renal function assessed by creatinine clearance was similar for both groups. Graft loss occurred in 7 vs. 4 patients on preemptive versus prophylactic therapy (P>0.05). Tolerability was similar for both treatment groups.
Conclusions. Oral valganciclovir prophylaxis significantly reduces CMV infection and disease, particularly for D+/R+ patients. Hence, our study supports routine prophylaxis for all D+/R+ recipients.

Tuesday, November 29, 2011

Utility of Colonoscopy in the Evaluation of Diarrhea in Solid Organ Transplant Recipients

Utility of Colonoscopy in the Evaluation of Diarrhea in Solid Organ Transplant Recipients: Background. Diarrhea is common in solid organ transplant recipients. Colonoscopy with random biopsies is performed frequently in the diagnostic evaluation of the posttransplant population with diarrhea. The purpose of this study was to determine the sensitivity of colonoscopy with random biopsy in determining a specific diagnosis and changing management in solid organ transplant recipients with diarrhea.
Methods. From October 1996 to June 2008, 88 patients were identified who had undergone solid organ transplantation and subsequently underwent colonoscopy for an indication of "diarrhea." These patient's electronic medical records were reviewed to determine patient demographics, laboratory results, findings on colonoscopy and histopathology, and any subsequent diagnoses made and management changes in relation to the diarrhea.
Results. Eighty-eight patients (mean age 54 years, 65% male) underwent colonoscopy a mean of 69 months after transplantation. Abnormal colonoscopic findings were seen in 16 (18.2%) patients. Histopathology was abnormal in 17/80 (21.3%). However, only eight (9.1%) had findings on colonoscopy or pathologic condition that led to specific diagnosis being made. In addition, only nine (10.2%) patients had a change in medical management as a direct result of colonoscopy with biopsy.
Conclusion. Although colonoscopic or histopathologic abnormalities are common in the solid organ transplant recipient with diarrhea, the findings rarely lead to a specific diagnosis or management change. Colonoscopy with biopsy should be performed only after noninvasive testing for infectious diarrhea and a thorough review and adjustment of medications. In many patients, a trial of antidiarrheal medication is warranted before colonoscopy.
(C) 2009 Lippincott Williams & Wilkins, Inc.

Alemtuzumab Versus Interleukin-2 Receptor Antibodies Induction in Living Donor Kidney Transplantation

Alemtuzumab Versus Interleukin-2 Receptor Antibodies Induction in Living Donor Kidney Transplantation: Background. Alemtuzumab use has been increasing in kidney transplantation. We aimed to compare posttransplantation outcomes between alemtuzumab and interleukin-2 receptor antibodies (IL-2RA) in living donor kidney transplant recipients in the United States.
Methods. Organ Procurement Transplant Network/United Network of Organ Sharing data, as of August 2007, were used to identify all living donor kidney transplants performed in adults in the United States from 2003 to 2006 where induction therapy with alemtuzumab or IL-2RA (daclizumab or basiliximab) was used. Primary outcomes included incidence of acute rejection, graft survival, and patient survival.

Pneumocystis jirovecii pneumonia is rare in renal transplant recipients receiving only one month of prophylaxis

Pneumocystis jirovecii pneumonia is rare in renal transplant recipients receiving only one month of prophylaxis:

Abstract:

Prophylaxis against Pneumocystis jirovecii pneumonia (PCP) is recommended for at least 4–12 months after solid organ transplant. In our center, renal transplant recipients receive only 1 month of post-transplant trimethoprim–sulfamethoxazole, which also may provide limited protection against Nocardia. We identified only 4 PCP cases and 4 Nocardia cases in 1352 patients receiving renal and renal-pancreas transplant from 2003 to 2009 at the University of Michigan Health System.

Pneumocystis jirovecii pneumonia in kidney transplantation

Pneumocystis jirovecii pneumonia in kidney transplantation:

Abstract:

Pneumocystis jirovecii pneumonia (PCP) remains an important cause of morbidity and mortality in immunocompromised renal transplant recipients. In recent years, PCP outbreaks in renal transplant centers have been reported in many countries. Person-to-person transmission between PCP patients and other recipients lacking prophylaxis is one of the possible sources of infection. To prevent infection, effective prophylaxis in susceptible patients is recommended. Trimethoprim-sulfamethoxazole (TMP-SMX) is the most effective drug for PCP prophylaxis, but its recommended duration of use after transplantation varies among the different guidelines. The European Renal Association recommends a prophylaxis period of 4 months after transplantation, the American Society of Transplantation (AST) 6–12 months, and the Kidney Disease Improving Global Outcomes guidelines 3–6 months. Lifelong prophylaxis with TMP-SMX is not recommended in renal transplant recipients; however, in many cases, PCP has occurred after the recommended prophylaxis periods after transplantation. In this minireview, we discuss the risk factors including environmental-nosocomial exposure; state-of-the-art diagnosis, treatment, prophylaxis and isolation; and references to the AST 2009 guidelines with the aim of integrating our experience with PCP outbreaks into recent reports, and we discuss how renal transplant recipients can be protected from PCP.

Valganciclovir Prophylaxis Versus Preemptive Therapy in Cytomegalovirus-Positive Renal Allograft Recipients: 1-Year Results of a Randomized Clinical Trial

Valganciclovir Prophylaxis Versus Preemptive Therapy in Cytomegalovirus-Positive Renal Allograft Recipients: 1-Year Results of a Randomized Clinical Trial: Background. Cytomegalovirus (CMV) prevention can be achieved by prophylaxis or preemptive therapy. We performed a prospective randomized trial to determine whether renal transplant recipients with a positive CMV serostatus (R+) had a higher rate of CMV infection and disease after transplantation when treated preemptively for CMV infection, compared with primary valganciclovir prophylaxis.
Methods. Prophylaxis was 2x450 mg oral valganciclovir/day for 100 days; preemptive patients were monitored by CMV-polymerase chain reaction (PCR), and after a positive PCR test received 2x900 mg valganciclovir/day for at least 14 days followed by secondary prophylaxis. Valganciclovir dosage was adjusted according to renal function. Patients are followed up for 5 years and initial 12-month data are presented. Two hundred and ninety-six recipients were analyzed (168 donor/recipient seropositive [D+/R+], 128 donor seronegative/recipient seropositive [D-/R+]; 146 receiving prophylaxis and 150 preemptive therapy).

Early Subclinical Rejection as a Risk Factor for Late Chronic Humoral Rejection

Early Subclinical Rejection as a Risk Factor for Late Chronic Humoral Rejection: Background. Subclinical rejection and interstitial fibrosis and tubular atrophy (IF/TA) in protocol biopsies are associated with outcome. We study the relationship between histologic lesions in early protocol biopsies and histologic diagnoses in late biopsies for cause.
Materials and Methods. Renal transplants with a protocol biopsy performed within the first 6 months posttransplant between 1988 and 2006 were reviewed. Biopsies were evaluated according to Banff criteria, and C4d staining was available in biopsies for cause.

Donor Desmopressin Is Associated With Superior Graft Survival After Kidney Transplantation

Donor Desmopressin Is Associated With Superior Graft Survival After Kidney Transplantation: Background. A recent randomized trial showed that pretreatment of the brain-dead donor with low-dose dopamine improves immediate kidney graft function, by limiting injury from cold storage (ClinicalTrials.gov Identifier: NCT00115115). This study determines whether donor exposure to desmopressin (1-deamino-8-d-arginine-vasopressin [DDAVP]) before organ retrieval affects renal transplant outcome.
Methods. This retrospective multicenter cohort study, nested in the database of the dopamine trial, includes 264 deceased heart-beating donors with confirmed brain death and corresponding 487 renal allograft recipients transplanted at 60 European centers between March 2004 and August 2007. We assessed differences in delayed graft function, biopsy-proven acute rejections, and 2-year kidney graft survival in recipients of a DDAVP-exposed versus unexposed graft.

Impact of Accidental Discovery of Renal Cell Carcinoma at Time of Renal Transplantation on Patient or Graft Survival

Impact of Accidental Discovery of Renal Cell Carcinoma at Time of Renal Transplantation on Patient or Graft Survival: Background. Renal tumors are common in the pretransplant end-stage renal disease population. Their impact on transplant outcome has not been well addressed.
Methods. This study is a retrospective follow-up observational study conducted in 258 renal transplant recipients. All patients had an ipsilateral native nephrectomy at the time of transplantation. We reviewed the histopathology of all native nephrectomies to gauge the prevalence of renal cell carcinoma (RCC) and to investigate the impact of accidental discovery of RCC on graft and patient outcome.

Understanding the Causes of Kidney Transplant Failure: The Dominant Role of Antibody-Mediated Rejection and Nonadherence

Understanding the Causes of Kidney Transplant Failure: The Dominant Role of Antibody-Mediated Rejection and Nonadherence:
We prospectively studied kidney transplants that progressed to failure after a biopsy for clinical indications, aiming to assign a cause to every failure. We followed 315 allograft recipients who underwent indication biopsies at 6 days to 32 years posttransplant. Sixty kidneys progressed to failure in the follow-up period (median 31.4 months). Failure was rare after T-cell–mediated rejection and acute kidney injury and common after antibody-mediated rejection or glomerulonephritis.

Tuberculosis following kidney transplantation: clinical features and outcome. A French multicentre experience in the last 20 years

Tuberculosis following kidney transplantation: clinical features and outcome. A French multicentre experience in the last 20 years:
Background. Kidney transplant recipients are at high risk of opportunistic infection. The aims of this study were to describe the epidemiology, clinical features and prognosis of Tuberculosis (TB) in kidney transplant recipients.
Methods. Retrospective observational study conducted in 14 French transplant centres involving all cases of TB that occurred in kidney transplant recipients between 1986 and 2006.

Epidemiology of Cytomegalovirus Infection After Pancreas Transplantation

Epidemiology of Cytomegalovirus Infection After Pancreas Transplantation: Background. Epidemiology of cytomegalovirus (CMV) infection has not been comprehensively studied after all three types of pancreas transplant (PT) including simultaneous pancreas-kidney transplantation (SPK), pancreas transplantation alone (PTA), and pancreas after kidney transplantation (PAK).
Methods. We evaluated incidence, risk factors, and outcomes of CMV infection after pancreas transplant at our center from January 1, 1998, to December 31, 2009.

Thymoglobulin Versus Basiliximab Induction Therapy for Simultaneous Kidney-Pancreas Transplantation: Impact on Rejection, Graft Function, and Long-Term Outcome

Thymoglobulin Versus Basiliximab Induction Therapy for Simultaneous Kidney-Pancreas Transplantation: Impact on Rejection, Graft Function, and Long-Term Outcome: Background. Thymoglobulin (ATG) and basiliximab induction therapies are used by the majority of centers for pancreas transplantation today. Although both strategies have different mechanisms, there is a paucity of studies comparing them. We compared the efficacy and side effects of both methods in simultaneous pancreas-kidney (SPK) transplantation.
Methods. We analyzed 128 SPKs at our institution between January 2001 and August 2008. Forty-nine patients received basiliximab (40 mg), whereas 79 patients had ATG (5 mg/kg). Graft function, complications, rejection, and survival rates were analyzed.
Results. ATG versus basiliximab therapy was associated with decreased 3-month (6% vs. 21%; P=0.01) and 1-year (14% vs. 27%; P=0.049) rejection rate. Steroid-resistant rejections were decreased with ATG (3%) vs. basiliximab (14%) (P=0.01). In a univariate regression analysis, basiliximab induction was a risk factor for rejection (HR, 7.1; CI, 3.8–13). No differences were observed regarding complications and graft function up to 5 years. ATG versus basiliximab therapy resulted in identical 1-year (90% vs. 93%), 3-year (87% vs. 89%), and 5-year (78% vs. 83%) pancreas survival (P=0.7). No difference was observed in kidney survival after 1 year (99% vs. 98%), 3 years (97% vs. 98%), and 5 years (95% vs. 95%) (P=0.4).
Conclusions. ATG versus basiliximab induction therapy results in decreased acute cellular rejection in the first year after SPK with similar side effects. Long-term graft function and survival are not affected by induction regimen.

Randomized Trial of Dual Antibody Induction Therapy With Steroid Avoidance in Renal Transplantation

Randomized Trial of Dual Antibody Induction Therapy With Steroid Avoidance in Renal Transplantation: Background. Given our previous experience using dual-induction therapy with antithymocyte globulin (ATG)/daclizumab (Dac) (each with fewer doses than if used alone), we chose to compare two distinct dual-induction strategies.
Methods. Single-center, open-label randomized trial of 200 primary kidney transplant recipients was performed: (group I, n=100) ATG/Dac (3 ATG, 2 Dac doses) versus (group II, n=100) ATG/alemtuzumab (1 dose each), with maintenance consisting of reduced tacrolimus dosing (rTd), enteric-coated mycophenolate sodium (EC-MPS), and early corticosteroid withdrawal. One half of standard EC-MPS dosing was targeted in group II to avoid severe leukopenia previously seen with alemtuzumab. The goal in both arms was to achieve rapid and effective lymphocyte depletion while simultaneously allowing reduced maintenance immunosuppression. Primary endpoint was the incidence of biopsy-proven acute rejection (BPAR).
Results. With median follow-up of 38 months, there were no differences in BPAR rates: 14 of 100 vs. 13 of 100 (including borderline) and 10 of 100 vs. 9 of 100 (excluding borderline) in groups I and II, respectively (nonsignificant). Actuarial patient/graft survival at 48 months was 96%/91% in group I vs. 92%/83% in group II (N.S.). Mean estimated glomerular filtration rate (+/-standard error) at 36 months was 72.1+/-3.3 vs. 67.5+/-3.3 in groups I and II (N.S.). Greater incidence of leukopenia occurred in group II at month 1 only (P=0.002). Percentages having EC-MPS withheld/discontinued due to leukopenia, gastrointestinal symptoms, and infection were 12 of 100, 7 of 100, and 0 of 100 in group I vs. 19 of 100, 0 of 100, and 2 of 100 in group II, respectively (P=0.01). Rates of new onset diabetes mellitus after transplantation and infections were equally low in both groups (no lymphoproliferative disorders were observed).
Conclusions. These two distinct dual-induction therapies with rTd, EC-MPS, and planned early corticosteroid withdrawal resulted in favorable rates of BPAR and all secondary outcomes.
(C) 2011 Lippincott Williams & Wilkins, Inc.

Prediction of Delayed Graft Function by Means of a Novel Web-Based Calculator: A Single-Center Experience

Prediction of Delayed Graft Function by Means of a Novel Web-Based Calculator: A Single-Center Experience:
Renal failure persisting after renal transplant is known as delayed graft function (DGF). DGF predisposes the graft to acute rejection and increases the risk of graft loss. In 2010, Irish et al. developed a new model designed to predict DGF risk. This model was used to program a web-based DGF risk calculator, which can be accessed via
http://www.transplantcalculator.com
. The predictive performance of this score has not been tested in a different population. We analyzed 342 deceased-donor adult renal transplants performed in our hospital. Individual and population DGF risk was assessed using the web-based calculator. The area under the ROC curve to predict DGF was 0.710 (95% CI 0.653–0.767, p < 0.001). The “goodness-of-fit” test demonstrates that the DGF risk was well calibrated (p = 0.309). Graft survival was significantly better for patients with a lower DGF risk (5-year survival 71.1% vs. 60.1%, log rank p = 0.036). The model performed well with good discrimination ability and good calibration to predict DGF in a single transplant center. Using the web-based DGF calculator, we can predict the risk of developing DGF with a moderate to high degree of certainty only by using information available at the time of transplantation.

Wednesday, October 19, 2011

Risk of Pneumocystis jiroveci pneumonia in patients long after renal transplantation

Risk of Pneumocystis jiroveci pneumonia in patients long after renal transplantation:
Background. Pneumocystis jiroveci pneumonia (PCP) is an important cause of morbidity and mortality in renal transplant recipients (RTRs). Chemoprophylaxis with trimethoprim/sulphamethoxazole is recommended during the early post-transplantation period, but the optimal duration has not been determined and a main drawback of chemoprophylaxis is the development of resistance of the commensal faecal flora. A cluster outbreak of PCP occurred in our outpatient Renal Transplant Unit. We aimed to investigate risk factors for PCP in RTRs to determine who should receive long-term chemoprophylaxis.

Summary of the British Transplantation Society Guidelines for the Prevention and Management of CMV Disease After Solid Organ Transplantation

Summary of the British Transplantation Society Guidelines for the Prevention and Management of CMV Disease After Solid Organ Transplantation: The third edition of the British Transplantation Society Guidelines for the Prevention and Management of CMV Disease after Solid Organ Transplantation was published in March 2011. This article summarizes the important changes and advances in management in this rapidly evolving field. The pros and cons of universal, or targeted anti-cytomegalovirus (CMV) prophylaxis, and pre-emptive anti-CMV therapy are discussed, especially with respect to advances in CMV polymerase chain reaction monitoring. The evidence for oral anti-CMV prophylaxis using valganciclovir is presented, together with a summary of the treatment of CMV disease and emerging fields such as CMV vaccination, CMV genotyping, and drug resistance.
(C) 2011 Lippincott Williams & Wilkins, Inc.

Thymoglobulin Versus Basiliximab Induction Therapy for Simultaneous Kidney-Pancreas Transplantation: Impact on Rejection, Graft Function, and Long-Term Outcome

Thymoglobulin Versus Basiliximab Induction Therapy for Simultaneous Kidney-Pancreas Transplantation: Impact on Rejection, Graft Function, and Long-Term Outcome: Background. Thymoglobulin (ATG) and basiliximab induction therapies are used by the majority of centers for pancreas transplantation today. Although both strategies have different mechanisms, there is a paucity of studies comparing them. We compared the efficacy and side effects of both methods in simultaneous pancreas-kidney (SPK) transplantation.
Methods. We analyzed 128 SPKs at our institution between January 2001 and August 2008. Forty-nine patients received basiliximab (40 mg), whereas 79 patients had ATG (5 mg/kg). Graft function, complications, rejection, and survival rates were analyzed.

Three-Year Outcomes from BENEFIT, a Randomized, Active-Controlled, Parallel-Group Study in Adult Kidney Transplant Recipients

Three-Year Outcomes from BENEFIT, a Randomized, Active-Controlled, Parallel-Group Study in Adult Kidney Transplant Recipients:
The clinical profile of belatacept in kidney transplant recipients was evaluated to determine if earlier results in the BENEFIT study were sustained at 3 years. BENEFIT is a randomized 3 year, phase III study in adults receiving a kidney transplant from a living or standard criteria deceased donor.

Human Herpes Virus 8 in Solid Organ Transplantation

Human Herpes Virus 8 in Solid Organ Transplantation: Human herpes virus 8 (HHV-8) is a geographically limited virus that causes neoplastic and nonneoplastic diseases predominantly in endemic regions. Primary HHV-8 infection, which is usually asymptomatic in immunocompetent individuals, result in lifelong latency. When the equilibrium between virus and host immunity is disturbed, such as after organ transplantation, HHV-8 may activate molecular pathways that drive oncogenesis.

Outcomes of Late Corticosteroid Withdrawal after Renal Transplantation in Patients Exposed to Tacrolimus and/or Mycophenolate Mofetil: Meta-Analysis of Randomized Controlled Trials

Outcomes of Late Corticosteroid Withdrawal after Renal Transplantation in Patients Exposed to Tacrolimus and/or Mycophenolate Mofetil: Meta-Analysis of Randomized Controlled Trials:
Background: Corticosteroids are increasingly used in renal transplant patients to minimize organ rejection after transplantation. In attempts to reduce corticosteroids adverse effects, transplant professionals are customary attempted to taper off, and permanently stop corticosteroids after few months of administration with other immunosuppressants.
Objective: To evaluate clinical benefits and risks of late corticosteroid withdrawal in renal transplant patients treated with tacrolimus (TAC) or mycophenolate mofetil (MMF), or both.
Methods: A meta-analysis was performed of published randomized controlled trials that reported outcomes in kidney transplant patients who were randomized to corticosteroids maintenance or late withdrawal under concomitant immunosuppression by TAC, MMF or both. Outcomes included acute graft rejection; graft failure rate; all-cause mortality; incidence of post-transplant diabetes; change in serum creatinine and total cholesterol; and change in pediatric standardized height z-score. PubMed and Google Scholar were used in literature search between 1999 and April 1, 2010. Data were combined using unweighted random effects model.
Results: Nine studies randomized 1907 patients met the inclusion criteria: TAC (n=1); MMF (n=6); both (n=2). Compared to maintenance therapy, late corticosteroid withdrawal was associated with 34% increase in the risk of acute graft rejection (95% CI for OR: 0.47–3.82); 35% and 5% reductions in the risk of graft failure and patient’s all-cause mortality (95% CI for OR: 0.26–1.60; 0.23–3.93, respectively); and 4% increase in post-transplant diabetes risk (95% CI for OR: 0.45–2.41). Late corticosteroid withdrawal was associated with substantial reduction in total cholesterol levels (mean difference: 18.1 mg/dL; 95% CI: 7.1–29.0 mg/dL), but did not reduce serum creatinine levels (‑0.00 mg/dL; 95% CI: ‑0.17 to 0.17). Stopping corticosteroids was associated with better pediatric growth outcomes.
Conclusion: Late corticosteroid withdrawal under TAC and/or MMF-lead immunosuppression after kidney transplantation could provide benefits in terms of total cholesterol, patient and graft survival, and pediatric growth. This strategy, however did not reduce the risk of acute graft rejection, post-transplant diabetes mellitus, and deterioration in serum creatinine levels.

Associations of Renal Function at 1-Year After Kidney Transplantation With Subsequent Return to Dialysis, Mortality, and Healthcare Costs

Associations of Renal Function at 1-Year After Kidney Transplantation With Subsequent Return to Dialysis, Mortality, and Healthcare Costs: Background. Improved early kidney transplant outcomes limit the contemporary utility of standard clinical endpoints. Quantifying the relationship of renal function at 1 year after transplant with subsequent clinical outcomes and healthcare costs may facilitate cost-benefit evaluations among transplant recipients.
Methods. Data for Medicare-insured kidney-only transplant recipients (1995–2003) were drawn from the United States Renal Data System. Associations of estimated glomerular filtration rate (eGFR) level at the first transplant anniversary with subsequent death-censored graft failure and patient death in posttransplant years 1 to 3 and 4 to 7 were examined by parametric survival analysis. Associations of eGFR with total health care costs defined by Medicare payments were assessed with multivariate linear regression.

Human Leukocyte Antigen Antibody-Incompatible Renal Transplantation: Excellent Medium-Term Outcomes With Negative Cytotoxic Crossmatch

Human Leukocyte Antigen Antibody-Incompatible Renal Transplantation: Excellent Medium-Term Outcomes With Negative Cytotoxic Crossmatch: Background. Human leukocyte antigen (HLA) antibody-incompatible renal transplantation has been increasingly performed since 2000 but with few data on the medium-term outcomes.
Methods. Between 2003 and 2011, 84 patients received renal transplants with a pretreatment donor-specific antibody (DSA) level of more than 500 in a microbead assay. Seventeen patients had positive complement-dependent cytotoxic (CDC) crossmatch (XM), 44 had negative CDC XM and positive flow cytometric XM, and 23 had DSA detectable by microbead only. We also reviewed 28 patients with HLA antibodies but no DSA at transplant. DSAs were removed with plasmapheresis pretransplant, and patients did not routinely receive antithymocyte globulin posttransplant.

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.

Monday, August 29, 2011

Comparing Outcomes Associated With Dose Manipulations of Enteric-Coated Mycophenolate Sodium Versus Mycophenolate Mofetil in Renal Transplant Recipients

Comparing Outcomes Associated With Dose Manipulations of Enteric-Coated Mycophenolate Sodium Versus Mycophenolate Mofetil in Renal Transplant Recipients: Background. This study assessed the incidence of reported gastrointestinal (GI) complications in patients treated with enteric-coated mycophenolate sodium (EC-MPS) versus mycophenolate mofetil (MMF) and to examine the impact of dose manipulations on biopsy-proven acute rejection (BPAR).
Methods. A retrospective study was conducted in 379 renal transplant recipients initiated on EC-MPS or MMF through 3-months posttransplant between the years of 2001 to 2007. Descriptive univariate analyses were used for comparisons of baseline characteristics and outcome measures between the cohorts. A Cox proportional hazards model was used to evaluate the time to a first BPAR event.

Histologic Recurrence of Henoch-Schonlein Purpura Nephropathy After Renal Transplantation on Routine Allograft Biopsy

Histologic Recurrence of Henoch-Schonlein Purpura Nephropathy After Renal Transplantation on Routine Allograft Biopsy: Background. Henoch-Schonlein Purpura nephropathy (HSPN) recurrence in renal transplant recipients (RTRs) has been reported in 35% of patients, leading in 11% of these patients to graft loss at 5 years. However, its true incidence is unknown. The aim of this study was to investigate this recurrence incidence using routine allograft biopsies (RBs).

Monday, August 22, 2011

Long-term follow up for anti-HLA donor specific antibodies postrenal transplantation: high immunogenicity of HLA class II graft molecules

Long-term follow up for anti-HLA donor specific antibodies postrenal transplantation: high immunogenicity of HLA class II graft molecules:

Summary

Τhe clinical significance of de novo post-transplant anti-HLA donor-specific antibodies (DSA) was evaluated using 4241 serum samples collected between 2000 and 2007 from 597 renal transplant recipients. Patients transplanted before December 1996 (n = 77) were included in the historic group and those transplanted thereafter (n = 520) were included in the study group.

Results of Repeat Renal Transplantation After Graft Loss From BK Virus Nephropathy

Results of Repeat Renal Transplantation After Graft Loss From BK Virus Nephropathy: Background. BK virus nephropathy (BKVN) is an important cause of renal graft loss in recent years. The aims of this study are to (1) describe the management of patients undergoing retransplantation after allograft loss in the setting of BKVN and (2) to identify risk factors for BK virus replication in the retransplant.

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.

Eculizumab in Acute Recurrence of Thrombotic Microangiopathy After Renal Transplantation

Eculizumab in Acute Recurrence of Thrombotic Microangiopathy After Renal Transplantation:
Renal thrombotic microangiopathy (TMA) is a severe complication of systemic lupus erythematosus (SLE), which is associated with the presence of antiphospholipid (aPL) antibodies. In its most fulminant form, TMA leads to a rapid and irreversible end-stage renal failure. Eculizumab, an anti-C5 monoclonal antibody, is a novel therapy of choice for patients with paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome.

Long-term Outcome of Renal Transplantation Patients with Henoch-Schonlein Purpura

Long-term Outcome of Renal Transplantation Patients with Henoch-Schonlein Purpura: SummaryBackground and objectives
Although Henoch-Schönlein purpura (HSP) is the most common form of renal vasculitis in childhood, progression to ESRD is rare, and there are few data on outcomes of renal transplantation in patients with HSP.
Design, setting, participants, & measurements: This is a matched retrospective cohort study of renal allografts using the United Network of Organ Sharing database (1987 to 2005). Of the 189,211 primary renal allografts, there were 339 with a diagnosis of HSP. The primary end point was allograft survival.

Impact of Cytomegalovirus Disease in D+/R– Kidney Transplant Patients Receiving 6 Months Low-Dose Valganciclovir Prophylaxis

Impact of Cytomegalovirus Disease in D+/R– Kidney Transplant Patients Receiving 6 Months Low-Dose Valganciclovir Prophylaxis:
Late-onset cytomegalovirus (CMV) disease remains common in CMV serology naïve kidney transplant patients of CMV serology positive organs (D+/R–) despite the use of antiviral prophylaxis. We studied clinical efficacy of 6-month low-dose valganciclovir (VGCV) prophylaxis, risk factors for late-onset CMV disease and its impact on kidney transplant outcomes. Between October 2005 and December 2009, 166 consecutive D+/R– kidney alone and simultaneous pancreas and kidney transplant patients received VGCV 450 mg daily for 6 months after transplantation. After a median follow-up of 3.2 years, 30 cases of CMV disease occurred within the first 2 years after transplantation with a cumulative incidence of 11.5 and 18.1% at 1 and 2 years, respectively.

Nocardia infection in kidney transplant recipients: case report and analysis of 66 published cases

Nocardia infection in kidney transplant recipients: case report and analysis of 66 published cases:
X. Yu, F. Han, J. Wu, Q. He, W. Peng, Y. Wang, H. Huang, H. Li, R. Wang, J. Chen. Nocardia infection in kidney transplant recipients: case report and analysis of 66 published cases. Transpl Infect Dis 2011: 13: 385–391. All rights reserved
Abstract: Nocardiosis is a rare but life-threatening opportunistic infection, especially in immune compromised patients, including kidney transplant recipients. Primary pulmonary infection is the most common clinical pattern, and can easily result in disseminated Nocardia infection if treatment therapy is not adequate at the beginning. In this article, we report a new case of disseminated nocardiosis (lungs, skin, and pericardium) after renal allograft transplantation. We also review the English literature published from 1980 to 2010 and analyze the clinical characteristics of nocardiosis in kidney transplant recipients.

Revisiting Traditional Risk Factors for Rejection and Graft Loss After Kidney Transplantation

Revisiting Traditional Risk Factors for Rejection and Graft Loss After Kidney Transplantation:
Single-antigen bead (SAB) testing permits reassessment of immunologic risk for kidney transplantation. Traditionally, high panel reactive antibody (PRA), retransplant and deceased donor (DD) grafts have been associated with increased risk. We hypothesized that this risk was likely mediated by (unrecognized) donor-specific antibody (DSA).

Monday, August 8, 2011

Cytomegalovirus Incidence Between Everolimus Versus Mycophenolate in De Novo Renal Transplants: Pooled Analysis of Three Clinical Trials

Cytomegalovirus Incidence Between Everolimus Versus Mycophenolate in De Novo Renal Transplants: Pooled Analysis of Three Clinical Trials: "
Everolimus (EVR) in heart and renal transplant (RTx) recipients may be associated with a decreased incidence of cytomegalovirus (CMV). A detailed analysis of the association between EVR versus mycophenolic acid (MPA) and CMV events has not been reported.

Rituximab-Induced Depletion of Anti-PLA2R Autoantibodies Predicts Response in Membranous Nephropathy

Rituximab-Induced Depletion of Anti-PLA2R Autoantibodies Predicts Response in Membranous Nephropathy: "
Autoantibodies to the M-type phospholipase A2 receptor (PLA2R) are sensitive and specific for idiopathic membranous nephropathy. The anti-B cell agent rituximab is a promising therapy for this disease, but biomarkers of early response to treatment currently do not exist. Here, we investigated whether levels of anti-PLA2R correlate with the immunological activity of membranous nephropathy, potentially exhibiting a more rapid response to treatment than clinical parameters such as proteinuria.

Efficacy and Safety of Early Cyclosporine Conversion to Sirolimus with Continued MMF—Four-Year Results of the Postconcept Study

Efficacy and Safety of Early Cyclosporine Conversion to Sirolimus with Continued MMF—Four-Year Results of the Postconcept Study: "
Calcineurin inhibitor (CNI) withdrawal has been used as a strategy to improve renal allograft function. We previously reported that conversion from cyclosporine A (CsA) to sirolimus (SRL) 3 months after transplantation significantly improved renal function at 1 year. In the Postconcept trial, 77 patients in the SRL group and 85 in the CsA group were followed for 48 months.

Steroids and Recurrent IgA Nephropathy After Kidney Transplantation

Steroids and Recurrent IgA Nephropathy After Kidney Transplantation: "
We studied the impact of steroid use on kidney graft loss due to recurrent IgA nephropathy (IgAN). We used data from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) to conduct a survival analysis of adult recipients of a first kidney transplant for IgAN who received a graft between 1988 and 2007. Predictors of graft loss due to recurrent IgAN were analyzed in a competing risk survival analysis with steroid use modeled as a time-varying covariate.

Thursday, July 28, 2011

Pregnancy Outcomes in Kidney Transplant Recipients: A Systematic Review and Meta-Analysis

Pregnancy Outcomes in Kidney Transplant Recipients: A Systematic Review and Meta-Analysis: "
Approximately 50 000 women of reproductive age in the United States are currently living after kidney transplantation (KT), and another 2800 undergo KT each year. Although KT improves reproductive function in women with ESRD, studies of post-KT pregnancies are limited to a few voluntary registry analyses and numerous single-center reports. To obtain more generalizable inferences, we performed a systematic review and meta-analysis of articles published between 2000 and 2010 that reported pregnancy-related outcomes among KT recipients.

Tuesday, July 26, 2011

Lower Malignancy Rates in Renal Allograft Recipients Converted to Sirolimus-Based, Calcineurin Inhibitor-Free Immunotherapy: 24-Month Results From the CONVERT Trial

Lower Malignancy Rates in Renal Allograft Recipients Converted to Sirolimus-Based, Calcineurin Inhibitor-Free Immunotherapy: 24-Month Results From the CONVERT Trial: "Background. Long-term immunosuppression imposes increased malignancy risk in renal allograft recipients, significantly contributing to overall morbidity and mortality. This study examined malignancy rates in renal allograft recipients at 2 years after conversion to a sirolimus (SRL)-based, calcineurin inhibitor (CNI)-free regimen.
Methods. This open-label, randomized, multicenter study (the CONVERT Trial) randomly assigned 830 patients to SRL conversion (n=555) or CNI continuation (n=275). Patients with history of posttransplant lymphoproliferative disease or known/suspected malignancy within 5 years before screening were excluded. As part of standard safety measurements, subjects were monitored for any malignancy occurrence; both skin and nonskin malignancies were reported, even if the patient discontinued from the therapy. Malignancy rates were analyzed based on exposure time to study drugs (i.e., number of events per 100 person-years of follow-up).

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.

A Multicenter Experience With Generic Tacrolimus Conversion

A Multicenter Experience With Generic Tacrolimus Conversion: "Background. The first generic tacrolimus product gained Food and Drug Administration approval in August 2009. This prospective, observational trial sought to determine the need for dose titrations and measure drug cost savings on conversion to generic tacrolimus.
Methods. Transplant recipients on stable tacrolimus doses were converted from brand to generic tacrolimus on a mg:mg basis. Data were collected at the time of generic conversion (study arm) and at a time point exactly 6 months before conversion (control arm) for all subjects.

Monday, July 18, 2011

Conversion of Long-Term Kidney Transplant Recipients From Calcineurin Inhibitor Therapy to Everolimus: A Randomized, Multicenter, 24-Month Study

Conversion of Long-Term Kidney Transplant Recipients From Calcineurin Inhibitor Therapy to Everolimus: A Randomized, Multicenter, 24-Month Study: "Background. Benefits of conversion from calcineurin inhibitor (CNI) to mammalian target of rapamycin inhibitor-based immunosuppression in long-term kidney transplant patients remain uncertain.
Methods. ASCERTAIN was a 24-month, open-label, multicenter study. Kidney transplant patients more than 6 months posttransplant receiving CNI (baseline glomerular filtration rate [GFR] 30-70 mL/min/1.73 m2) were randomized to everolimus with CNI elimination (n=127) or CNI minimization (n=144), or continued CNI unchanged (controls, n=123) to assess the effect on measured GFR at month 24 after randomization.

Improved Rejection Prophylaxis With an Initially Intensified Dosing Regimen of Enteric-Coated Mycophenolate Sodium in De Novo Renal Transplant Recipients

Improved Rejection Prophylaxis With an Initially Intensified Dosing Regimen of Enteric-Coated Mycophenolate Sodium in De Novo Renal Transplant Recipients: "Background. Approximately half of cyclosporine A-treated renal transplant recipients do not reach sufficient mycophenolic acid (MPA) exposure in the first weeks posttransplantation with standard MPA dosing regimens.

Incidence and Outcomes of Ganciclovir-Resistant Cytomegalovirus Infections in 1244 Kidney Transplant Recipients

Incidence and Outcomes of Ganciclovir-Resistant Cytomegalovirus Infections in 1244 Kidney Transplant Recipients: "Background. Cytomegalovirus (CMV) infections in kidney transplant recipients are in most cases successfully treated with oral valganciclovir (VGCV). However, in a few percent of patients, mutations in the UL 97 or UL 54 gene lead to drug resistance.
Methods. We investigated the incidence and outcomes of ganciclovir-resistant CMV viremia in all 1244 kidney recipients transplanted at our center from 2004 through 2008. CMV DNAemia was monitored in all patients at least weekly, and patients who were positive were treated preemptively with VGCV (900 mg once daily).

Long-Term Outcome in Kidney Transplant Recipients Over 70 Years in the Eurotransplant Senior Kidney Transplant Program: A Single Center Experience

Long-Term Outcome in Kidney Transplant Recipients Over 70 Years in the Eurotransplant Senior Kidney Transplant Program: A Single Center Experience: "Background. Kidney transplantation in the elderly is complicated by comorbidities and a higher incidence of death. The Eurotransplant Senior Program (ESP) has been established to allocate kidneys from older donors to the increasing number of older recipients. In this retrospective, single center data analysis, we compare the outcome of recipients older than 70 years with younger recipients transplanted under the ESP protocol.

A Prospective Longitudinal Study Evaluating the Usefulness of a T-Cell-Based Assay for Latent Tuberculosis Infection in Kidney Transplant Recipients

A Prospective Longitudinal Study Evaluating the Usefulness of a T-Cell-Based Assay for Latent Tuberculosis Infection in Kidney Transplant Recipients: "
We evaluated whether ELISPOT assay can predict tuberculosis (TB) development in kidney-transplantation (KT) recipients with a negative tuberculin skin test (TST). All adult patients admitted to a KT institute between June 2008 and December 2009 were enrolled; TB development after KT was observed between June 2008 and December 2010. Isoniazid (INH) was given to those patients with positive TST or clinical risk factors for latent TB infection (LTBI). ELISPOT assay was performed on all patients, and TB development after KT was observed by a researcher blinded to the results of ELISPOT.

Thursday, July 7, 2011

Efficacy and Safety of Conversion from Twice-daily to Once-daily Tacrolimus in a Large Cohort of Stable Kidney Transplant Recipients

Efficacy and Safety of Conversion from Twice-daily to Once-daily Tacrolimus in a Large Cohort of Stable Kidney Transplant Recipients: "
Prolonged-release tacrolimus was developed to provide a more convenient once-daily dosing that could improve patient adherence. We conducted a multicenter, prospective, observational, 12-month study to describe the efficacy, safety and patient preference of conversion from tacrolimus twice-daily to once-daily formulation in stable kidney transplant recipients in routine clinical practice. Conversion was made on a 1 mg: 1 mg basis (1 mg: 1.1 mg in patients with trough levels <6 ng/mL).

The ORION Study: Comparison of Two Sirolimus-Based Regimens versus Tacrolimus and Mycophenolate Mofetil in Renal Allograft Recipients

The ORION Study: Comparison of Two Sirolimus-Based Regimens versus Tacrolimus and Mycophenolate Mofetil in Renal Allograft Recipients: "
Safety and efficacy of two sirolimus (SRL)-based regimens were compared with tacrolimus (TAC) and mycophenolate mofetil (MMF). Renal transplantation recipients were randomized to Group 1 (SRL+TAC; week 13 TAC elimination [n = 152]), Group 2 (SRL + MMF [n = 152]) or Group 3 (TAC + MMF [n = 139]). Group 2, with higher-than-expected biopsy-confirmed acute rejections (BCARs), was sponsor-terminated; therefore, Group 2 two-year data were limited. At 1 and 2 years, respectively, graft (Group 1: 92.8%, 88.5%; Group 2: 90.6%, 89.9%; Group 3: 96.2%, 95.4%) and patient (Group 1: 97.3%, 94.4%; Group 2: 95.2%, 94.5%; Group 3: 97.0%, 97.0%) survival rates were similar. One- and 2-year BCAR incidence was: Group 1, 15.2%, 17.4%; Group 2, 31.3%, 32.8%; Group 3, 8.2%, 12.3% (Group 2 vs. 3, p < 0.001). Mean 1- and 2-year modified intent-to-treat glomerular filtration rates (mL/min) were similar. Primary reason for discontinuation was adverse events (Group 1, 34.2%; Group 2, 33.6%; Group 3, 22.3%; p < 0.05). In Groups 1 and 2, delayed wound healing and hyperlipidemia were more frequent. One-year post hoc analysis of new-onset diabetes posttransplantation was greater in TAC recipients (Groups 1 and 3 vs. 2, 17% vs. 6%; p = 0.004). Between-group malignancy rates were similar. The SRL-based regimens were not associated with improved outcomes for kidney transplantation patients.
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Interstitial Fibrosis Evolution on Early Sequential Screening Renal Allograft Biopsies Using Quantitative Image Analysis.

Interstitial Fibrosis Evolution on Early Sequential Screening Renal Allograft Biopsies Using Quantitative Image Analysis.: "Servais A, Meas-Yedid V, Noël LH, et al.
Interstitial Fibrosis Evolution on Early Sequential Screening Renal Allograft Biopsies Using Quantitative Image Analysis. [JOURNAL ARTICLE]
Am J Transplant 2011 Jun 14.
Abstract | Full Citation | Publisher Full Text | Find Related Articles "

The Impact of Conversion From Prograf to Generic Tacrolimus in Liver and Kidney Transplant Recipients With Stable Graft Function.

The Impact of Conversion From Prograf to Generic Tacrolimus in Liver and Kidney Transplant Recipients With Stable Graft Function.: "Momper JD, Ridenour TA, Schonder KS, et al.
The Impact of Conversion From Prograf to Generic Tacrolimus in Liver and Kidney Transplant Recipients With Stable Graft Function. [JOURNAL ARTICLE]
Am J Transplant 2011 Jun 30.
Abstract | Full Citation | Publisher Full Text | Find Related Articles "

Tuesday, July 5, 2011

Posttransplant sCD30 as a Predictor of Kidney Graft Outcome

Posttransplant sCD30 as a Predictor of Kidney Graft Outcome: "Background. Reliable markers for assessing the biological effect of immunosuppressive drugs and identification of transplant recipients at risk of developing rejection are not available.
Methods. In a prospective multicenter study, we investigated whether posttransplant measurement of the T-cell activation marker soluble CD30 (sCD30) can be used for estimating the risk of graft loss in kidney transplant recipients. Pre- and posttransplant sera of 2322 adult deceased-donor kidney recipients were tested for serum sCD30 content using a commercial enzyme-linked immunosorbent assay.

Associations of Renal Function at 1-Year After Kidney Transplantation With Subsequent Return to Dialysis, Mortality, and Healthcare Costs

Associations of Renal Function at 1-Year After Kidney Transplantation With Subsequent Return to Dialysis, Mortality, and Healthcare Costs: "Background. Improved early kidney transplant outcomes limit the contemporary utility of standard clinical endpoints. Quantifying the relationship of renal function at 1 year after transplant with subsequent clinical outcomes and healthcare costs may facilitate cost-benefit evaluations among transplant recipients.
Methods. Data for Medicare-insured kidney-only transplant recipients (1995–2003) were drawn from the United States Renal Data System. Associations of estimated glomerular filtration rate (eGFR) level at the first transplant anniversary with subsequent death-censored graft failure and patient death in posttransplant years 1 to 3 and 4 to 7 were examined by parametric survival analysis. Associations of eGFR with total health care costs defined by Medicare payments were assessed with multivariate linear regression.

Saturday, June 25, 2011

Risk factors for Pneumocystis jirovecii pneumonia in kidney transplant recipients and appraisal of strategies for selective use of chemoprophylaxis

Risk factors for Pneumocystis jirovecii pneumonia in kidney transplant recipients and appraisal of strategies for selective use of chemoprophylaxis: "
M.G.J. de Boer, F.P. Kroon, S. le Cessie, J.W. de Fijter, J.T. van Dissel. Risk factors for Pneumocystis jirovecii pneumonia in kidney transplant recipients and appraisal of strategies for selective use of chemoprophylaxis. Transpl Infect Dis 2011. All rights reserved
Abstract: Risk stratification-based duration of trimethoprim-sulfamethoxazole (TMP-SMX) chemoprophylaxis to prevent Pneumocystis pneumonia (PCP) in kidney transplant recipients is not a universally adapted strategy and supporting evidence-based sources are limited. We performed a large retrospective study to identify risk factors for PCP in kidney transplant recipients and to define parameters for use in clinical prophylaxis guidelines. Fifty consecutive patients with confirmed PCP and 2 time-matched controls per case were enrolled.

Friday, June 3, 2011

Antibody-Mediated Rejection After Alemtuzumab Induction: Incidence, Risk Factors, and Predictors of Poor Outcome

Antibody-Mediated Rejection After Alemtuzumab Induction: Incidence, Risk Factors, and Predictors of Poor Outcome: "Background. Antibody-mediated rejection (AMR) is associated with allograft loss. Identification of factors associated with poor outcome has not been extensively studied.
Methods. We retrospectively studied 469 patients who received a negative crossmatch renal transplant with alemtuzumab induction. Forty-eight of 469 (10.2%) patients were treated for AMR. Thirty of 48 (62.5%) of the cases fulfilled the Banff criteria for definite AMR, whereas 18 of 48 (37.5%) were categorized as suspicious for AMR (tissue injury with C4d staining or donor-specific antibodies [DSAbs]). Sensitization, high human leukocyte antigen, and -DR mismatch were risk factors for the development of AMR (P=0.0016, 0.001, and 0.012, respectively).

Tuesday, May 31, 2011

Effect of Kidney Transplantation on Outcomes among Patients with Hepatitis C

Effect of Kidney Transplantation on Outcomes among Patients with Hepatitis C: "
The long-term outcome of kidney transplantation in patients infected with hepatitis C virus (HCV) and end stage renal disease (ESRD) is not well described. We retrospectively identified 230 HCV-infected patients using enzyme immunoassay and nucleic acid testing obtained during the transplant evaluation. Of 207 patients who had a liver biopsy before transplant, 44 underwent 51 follow-up liver biopsies at approximately 5-year intervals either while on the waitlist for a kidney or after kidney transplantation. Advanced fibrosis was present in 10% of patients biopsied, identifying a population that may warrant consideration for combined liver-kidney transplantation. Kidney transplantation does not seem to accelerate liver injury; 77% of kidney recipients who underwent follow-up biopsies showed stable or improved liver histology.

Early Loss of Peritubular Capillaries after Kidney Transplantation

Early Loss of Peritubular Capillaries after Kidney Transplantation: "
Inflammation, interstitial fibrosis (IF), and tubular atrophy (TA) precede chronic transplant dysfunction, which is a major cause of renal allograft loss. There is an association between IF/TA and loss of peritubular capillaries (PTCs) in advanced renal disease, but whether PTC loss occurs in an early stage of chronic transplant dysfunction is unknown. Here, we studied PTC number, IF/TA, inflammation, and renal function in 48 patients who underwent protocol biopsies.

Thursday, May 26, 2011

Randomized Trial of Mycophenolate Mofetil Versus Enteric-Coated Mycophenolate Sodium in Primary Renal Transplantation With Tacrolimus and Steroid Avoidance: Four-Year Analysis

Randomized Trial of Mycophenolate Mofetil Versus Enteric-Coated Mycophenolate Sodium in Primary Renal Transplantation With Tacrolimus and Steroid Avoidance: Four-Year Analysis: "Background. Our single-center, open-labeled randomized trial of 150 adult, primary kidney transplant recipients receiving 2 g mycophenolate mofetil (group A, n=75) versus 1.440 g enteric-coated mycophenolate sodium (group B, n=75), with reduced maintenance tacrolimus dosing, steroid elimination at 1 week, and combined rabbit antithymocyte globulin/daclizumab induction, previously showed at 1 year posttransplant low biopsy-proven acute rejection (BPAR), acceptably high renal function, and no differences in incidence of symptomatic gastrointestinal (GI) side effects between the two groups. This report includes 3 additional years of follow-up with similar endpoints as in the original study.
Methods. Rates of developing first BPAR, graft failure (death censored and uncensored), death, and adverse events (GI toxicity, infections requiring hospitalization, and new onset diabetes mellitus after transplantation) during the first 48 months posttransplant were compared between the two groups using an intent-to-treat approach.

Effect of Human Leukocyte Antigen Compatibility on Kidney Graft Survival: Comparative Analysis of Two Decades

Effect of Human Leukocyte Antigen Compatibility on Kidney Graft Survival: Comparative Analysis of Two Decades: "Background. Based on an analysis of United Network for Organ Sharing data, it was reported that the influence of human leukocyte antigen (HLA) matching in renal transplantation has diminished in recent years, prompting the suggestion that donor kidney allocation algorithms should be revised.
Methods. We compared the impact of HLA matching on kidney graft survival during the decades 1985-1994 and 1995-2004 using the data of the Collaborative Transplant Study. Results for the last 5 years (2000-2004) were analyzed separately in addition. Multivariate Cox regression analysis was used to account for the influence of confounders.
Results. Our results show that, while graft survival rates have improved overall over time, the relative impact of HLA matching on the graft survival rate has remained strong and highly significant. Both the need for posttransplant rejection treatment and the graft survival rates showed statistically highly significant associations with HLA matching regardless of the interval analyzed (P<0.001).
Conclusions. We conclude that HLA mismatches significantly influence the outcome of kidney transplants and that kidney exchange programs for the purpose of achieving better HLA matches continue to be meaningful.
(C) 2007 Lippincott Williams & Wilkins, Inc."

Monday, May 23, 2011

Preemptive versus prophylactic protocol to prevent cytomegalovirus infection after renal transplantation: a meta-analysis and systematic review of randomized controlled trials

Preemptive versus prophylactic protocol to prevent cytomegalovirus infection after renal transplantation: a meta-analysis and systematic review of randomized controlled trials: "
L.-F. Zhang, Y.-T. Wang, J.-H. Tian, K.-H. Yang, J.-Q. Wang. Preemptive versus prophylactic protocol to prevent cytomegalovirus infection after renal transplantation: a meta-analysis and systematic review of randomized controlled trials. Transpl Infect Dis 2011. All rights reserved
Objective. This review was conducted to assess the efficacy of preemptive versus prophylactic protocols for the prevention and treatment of cytomegalovirus (CMV) infection and disease after renal transplantation.
Methods. PubMed, EMBASE, the Cochrane Library, SCI, the China Journal Full-text Database, the Chinese Biomedical Database, the Chinese Scientific Journals Full-text Database, and the CMA Digital Periodicals were searched to collect randomized controlled trials (RCTs) of preemptive versus prophylactic protocols for the prevention and treatment of CMV infections after renal transplantation (up to April 2010). Two reviewers independently extracted data using a designed extraction form. The quality of the included trials was evaluated according to the Cochrane Handbook. RevMan 5.0 software was used for data analysis.

Sunday, May 22, 2011

Alemtuzumab Induction in Renal Transplantation

Alemtuzumab Induction in Renal Transplantation: (N Engl J Med 2011)


BACKGROUND

There are few comparisons of antibody induction therapy allowing early glucocorticoid withdrawal in renal-transplant recipients. The purpose of the present study was to compare induction therapy involving alemtuzumab with the most commonly used induction regimens in patient populations at either high immunologic risk or low immunologic risk.

METHODS

In this prospective study, we randomly assigned patients to receive alemtuzumab or conventional induction therapy (basiliximab or rabbit antithymocyte globulin). Patients were stratified according to acute rejection risk, with a high risk defined by a repeat transplant, a peak or current value of panel-reactive antibodies of 20% or more, or black race. The 139 high-risk patients received alemtuzumab (one dose of 30 mg, in 70 patients) or rabbit antithymocyte globulin (a total of 6 mg per kilogram of body weight given over 4 days, in 69 patients). The 335 low-risk patients received alemtuzumab (one dose of 30 mg, in 164 patients) or basiliximab (a total of 40 mg over 4 days, in 171 patients). All patients received tacrolimus and mycophenolate mofetil and underwent a 5-day glucocorticoid taper in a regimen of early steroid withdrawal. The primary end point was biopsy-confirmed acute rejection at 6 months and 12 months. Patients were followed for 3 years for safety and efficacy end points.

Friday, May 20, 2011

Desmopressin Acetate in Percutaneous Ultrasound-Guided Kidney Biopsy: A Randomized Controlled Trial

Desmopressin Acetate in Percutaneous Ultrasound-Guided Kidney Biopsy: A Randomized Controlled Trial: "Background: Bleeding complications occur in one-third of percutaneous kidney biopsies and increase costs of the hospital stay. The aim of the study was to evaluate the effect of prebiopsy administration of desmopressin acetate versus placebo in the incidence of postbiopsy bleeding complications.Study Design: Double-blind randomized controlled clinical trial.Setting & Participants: We enrolled all patients with serum creatinine level ≤1.5 mg/dL and/or estimated glomerular filtration rate ≥60 mL/min/1.73 m2 and normal coagulation parameters undergoing ultrasound-guided biopsy of the native kidney in our unit from August 2008 to December 2009.Intervention:

Prophylactic Peritoneal Fenestration to Prevent Morbidity After Kidney Transplantation: A Randomized Study

Prophylactic Peritoneal Fenestration to Prevent Morbidity After Kidney Transplantation: A Randomized Study: "Background. Formation of lymphocele (accumulation of lymphatic fluid) is a common surgical complication following kidney transplantation. This open randomized trial evaluated the effect of prophylactic fenestration on lymphocele formation.
Methods. Adult recipients of kidney grafts from deceased donors were randomized to undergo peritoneal fenestration during the transplantation or to standard surgical procedure without fenestration. The incidence of symptomatic lymphocele in the two groups was compared at 1 year after transplantation. A protocol-based ultrasound examination was performed in the 1st, 5th, and 10th postoperative week. Any hypoechoic perirenal collection was registered.

Wednesday, May 18, 2011

Mammalian target of rapamycin signal inhibitors could play a role in the treatment of BK polyomavirus nephritis in renal allograft recipients

Mammalian target of rapamycin signal inhibitors could play a role in the treatment of BK polyomavirus nephritis in renal allograft recipients: "
A.I. Sánchez Fructuoso, N. Calvo, I. Perez-Flores, R. Valero, B. Rodríguez-Sánchez, D. García de Viedma, P. Muñoz, A. Barrientos. Mammalian target of rapamycin signal inhibitors could play a role in the treatment of BK polyomavirus nephritis in renal allograft recipients. Transpl Infect Dis 2011. All rights reserved
Abstract: BK virus (BKV) nephropathy is a common viral infection in renal transplant patients, with a prevalence of 1–9% at approximately 12 months after surgery. While it is widely agreed that reduction of immunosuppression should be the first intervention after diagnosis of BKV infection, there is no consensus on whether calcineurin inhibitors or antiproliferative drugs should be reduced first. Furthermore, target levels of immunosuppressive drugs are poorly defined, as are criteria for replacing one immunosuppressive agent with another.

Single-center experience with third and fourth kidney transplants

Single-center experience with third and fourth kidney transplants: "

Kidney retransplantation is often associated with a higher immunological risk than is primary renal transplantation. Faced with increasing organ shortage and growing waiting lists, results of kidney retransplantation are of particular interest. Fifty-six third and fourth kidney transplants were analyzed retrospectively. Parameters included patient and donor demographics, operative details, incidence of surgical, immunological and infectious complications and patient and graft survival. Patients receiving third kidney grafts had 1- and 5-year patient/graft survival rates of 97.4%/72.9% and 88.9%/53.6%, respectively. Episodes of acute rejection and delayed graft function were observed in 44% and 49% of these patients. Fourth kidney transplantation was associated with 1- and 2-year patient/graft survival rates of 84.8%/68.5% and 63.6%/47%, respectively. Acute rejection and delayed graft function occurred in 33% and in 60% of cases. Acceptable patient and graft survival may be achieved after third and fourth kidney transplantation. Graft losses in this sensitized population are mainly because of rejection. Profound immunosuppression may lead to major infectious problems.

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Monday, May 16, 2011

Malignancies after kidney transplantation: a 40-year single-center experience in Korea

Malignancies after kidney transplantation: a 40-year single-center experience in Korea: "

Cancer is a well-recognized complication of kidney transplantation (KT), but nearly almost all data have come from Western countries. The aim of this study was to determine the incidence, type, and risk factors of malignancy after KT in Korea. The 1695 patients who underwent KT between 1969 and 2009 were studied retrospectively.