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.