Outcomes of Clostridium difficile infection in recipients of solid abdominal organ transplants.

Knowledge of outcomes of Clostridium difficile infection (CDI) in solid organ transplant (SOT) recipients is limited. To evaluate this population, we undertook a retrospective cohort study of all recipients of kidney and liver transplants diagnosed with CDI at a single center over 14 yr. Data pertaining to all episodes of CDI were collected. Multivariate analysis using logistic regression was performed to determine independent predictors of clinical cure. Overall, 170 patients developed 215 episodes of CDI. Among these patients, 162 episodes (75%) were cured, and in 103 episodes (48%), patients were cured within 14 d. In a multivariate analysis, lack of clinical cure at 14 d was predicted by recurrent episode (0.21, 95% CI 0.06-0.72, p = 0.0128), treatment with vancomycin (OR 0.27, 95% CI 0.1-0.74, p = 0.011), vasopressor support (OR 0.23, 95% CI 0.07-0.76, p = 0.0161), and CDI before the year 2004 (OR 0.44, 95% CI 0.2-0.98, p = 0.0446). The latter three factors are likely markers for severity of illness. In this cohort, 13 patients (8%) died during hospitalization, and 49 patients (29%) died within one yr. No deaths were attributed to CDI. Recurrent episode was a major predictor of treatment failure, suggesting that research into development of therapeutic options for recurrent disease is needed.

Serum ß2-microglobulin at discharge predicts mortality and graft loss following kidney transplantation.

Serum ß(2)-microglobulin (ß(2)M), a novel marker of kidney function, predicts mortality and kidney failure in the general population, and its elevation following transplantation is a marker of acute rejection. The association between post-transplant serum ß(2)M and outcomes following kidney transplantation, however, is unknown. To help determine this, we conducted a retrospective cohort study of 2190 individuals receiving a primary kidney transplant with serum ß(2)M measured at discharge. A total of 452 deaths and 347 graft failures before death (669 total graft losses) occurred over a median of 4.1 years of follow-up. After adjustment, the highest quintile of ß(2)M (5.0 mg/l and above), compared with the lowest quintile (<2.3 mg/l), was associated with a hazard ratio of 4.6 (95% confidence interval 2.8, 7.5) for death, 4.1 (2.4, 7.0) for death-censored graft loss, and 3.8 (2.5, 5.6) for total graft loss. Serum ß(2)M was more strongly associated with each outcome than was serum creatinine. Higher serum ß(2)M at discharge was independently associated with each outcome in models stratified by the presence of delayed graft function, donor type, or estimated glomerular filtration rate at discharge. Thus, serum ß(2)M at discharge is a potent predictor of long-term mortality and graft loss in kidney transplant recipients, providing information on allograft function beyond that of serum creatinine.

Increased C4d in post-reperfusion biopsies and increased donor specific antibodies at one-week post transplant are risk factors for acute rejection in mild to moderately sensitized kidney transplant recipients.

In order to define the intensity of immunosuppression, we examined risk factors for acute rejection in desensitization protocols that use baseline donor-specific antibody levels measured as mean fluorescence intensity (MFImax). The study included 146 patients transplanted with a negative flow crossmatch and a mean follow-up of 18 months with the majority (83%) followed for at least 1 year. At the time of transplant, mean-calculated panel-reactive antibody and MFImax ranged from 10.3-57.2% and 262-1691, respectively, between low- and high-risk protocols. Mean MFImax increased significantly from transplant to 1 week and 1 year. The incidence of acute rejection (mean 1.65 months) as a combination of clinical and subclinical rejection was 32%, including 14% cellular, 12% antibody-mediated, and 6% mixed rejection. In regression analyses, only C4d staining in post-reperfusion biopsies (hazard ratio 3.3, confidence interval 1.71-6.45) and increased specific antibodies at 1-week post transplant were significant predictors of rejection. A rise in MFImax by 500 was associated with a 2.8-fold risk of rejection. Thus, C4d staining in post-reperfusion biopsies and an early rise in donor specific antibodies after transplantation are risk factors for rejection in moderately sensitized patients.

Native kidney function following liver transplantation using calcineurin inhibitors: single-center analysis with 20 years of follow-up.

INTRODUCTION: The incidence of chronic kidney disease (CKD) in liver transplant recipients has been estimated to be from 18% to 28% at 10 yr after transplantation. As outcomes from liver transplantation continue to improve, long-term native kidney function in these recipients becomes more critical to patient survival. METHODS: We analyzed 1151 adult, deceased-donor, single-organ primary liver transplantations performed at our center between 7/17/84 and 12/31/07. Analysis of renal function was performed on 972 patients with liver allograft survival >1 yr. RESULTS: Kaplan-Meier analysis revealed that 3%, 7%, and 18% of liver transplant recipients with allograft survival >1 yr developed end-stage renal disease (ESRD) at five, 10, and 20 yr, respectively. Significant independent risk factors for ESRD included dialysis during the transplant hospitalization, the stage of CKD at one yr, hypercholesterolemia, non-Caucasian race, and hepatitis C as the primary indication for liver transplantation. The initial immunosuppression of essentially all recipients was a calcineurin inhibitor-based regimen. CONCLUSION: Close, long-term follow-up of liver transplant recipients permits optimal management of liver allograft and native renal function and can lead to excellent long-term outcomes despite a calcineurin inhibitor-based immunosuppressive regimen.

Homocysteine-lowering and cardiovascular disease outcomes in kidney transplant recipients: primary results from the Folic Acid for Vascular Outcome Reduction in Transplantation trial.

BACKGROUND: Kidney transplant recipients, like other patients with chronic kidney disease, experience excess risk of cardiovascular disease and elevated total homocysteine concentrations. Observational studies of patients with chronic kidney disease suggest increased homocysteine is a risk factor for cardiovascular disease. The impact of lowering total homocysteine levels in kidney transplant recipients is unknown. METHODS AND RESULTS: In a double-blind controlled trial, we randomized 4110 stable kidney transplant recipients to a multivitamin that included either a high dose (n=2056) or low dose (n=2054) of folic acid, vitamin B6, and vitamin B12 to determine whether decreasing total homocysteine concentrations reduced the rate of the primary composite arteriosclerotic cardiovascular disease outcome (myocardial infarction, stroke, cardiovascular disease death, resuscitated sudden death, coronary artery or renal artery revascularization, lower-extremity arterial disease, carotid endarterectomy or angioplasty, or abdominal aortic aneurysm repair). Mean follow-up was 4.0 years. Treatment with the high-dose multivitamin reduced homocysteine but did not reduce the rates of the primary outcome (n=547 total events; hazards ratio [95 confidence interval]=0.99 [0.84 to 1.17]), secondary outcomes of all-cause mortality (n=431 deaths; 1.04 [0.86 to 1.26]), or dialysis-dependent kidney failure (n=343 events; 1.15 [0.93 to 1.43]) compared to the low-dose multivitamin. CONCLUSIONS: Treatment with a high-dose folic acid, B6, and B12 multivitamin in kidney transplant recipients did not reduce a composite cardiovascular disease outcome, all-cause mortality, or dialysis-dependent kidney failure despite significant reduction in homocysteine level.

The impact of hepatitis C virus donor and recipient status on long-term kidney transplant outcomes: University of Wisconsin experience.

The survival benefit of transplanting hepatitis C (HCV)-positive donor kidneys into HCV-positive recipients remains uncertain. The purpose of this study was to assess the effect of HCV-status of the donor (D) kidney on the long-term outcomes in kidney transplant recipients (R). We evaluated 2169 consecutive recipients of deceased-donor kidney transplants performed between 1991 and 2007. The following HCV cohorts were identified: D-/R- (n = 1897), D-/R+ (n = 59), D+/R- (n = 118), and D+/R+ (n = 95). Patients were followed for a mean of 6.02 (standard deviation = 4.26) yr. In a mulitvariable Cox-proportional hazards model, D+/R+ cohort had significantly lower patient survival (adjusted-hazard ratio [HR] 2.1, 95% CI [1.4-2.9]) with respect to the reference D-/R- group, whereas mortality was not increased in D-/R+ group. The rate of graft loss was increased in both D+/R+ and D-/R+ but was comparable with each other (adjusted-HR 1.8, 95% CI [1.4-2.5]) vs. adjusted-HR 2.0, 95% CI [1.4-2.8], respectively). D-/R+ cohort experienced significantly higher rate of rejection (adjusted-HR 1.7, 95% CI [1.2-2.5]) and chronic allograft nephropathy (adjusted-HR 2.1, 95% CI [1.2-3.7]). Neither donor nor recipient HCV-status impacted the risk of recurrent or de novo GN. Transplanting HCV-positive kidneys as opposed to HCV-negative kidneys into HCV-positive recipients provided similar graft survival but compromised patient survival in the long term.

Complications associated with liver transplantation in the obese recipient.

The prevalence of the metabolic syndrome with attendant morbid obesity continues to increase nationwide. A concomitant increase in non-alcoholic steatohepatitis (NASH) and associated end-stage liver disease requiring transplantation is expected to parallel this trend. Between January 1, 1997 and December 31, 2008, our center performed 813 solitary adult deceased-donor liver transplants. Patients were divided into groups based on the World Health Organization International Classification of obesity. Patients within each obesity class were compared to normal weight recipients. Preoperative demographics among all groups were similar. NASH was more common in higher BMI groups. Operative time, blood product usage, ICU length of stay, infectious complications, and biliary complications requiring intervention were all higher in obese recipients. Deep venous thrombosis occurred more commonly in patients with Class III obesity. Patients with Class II obesity had lower patient (HR 1.82, CI 1.09-3.01, p=0.02) and allograft survival (HR 1.62, CI 1.02-2.65, p=0.04). Obesity class did not reach statistical significance on multivariate analysis. Despite increased technical operative challenges and medical complexities associated with increasing recipient BMI, morbid obesity in and of itself should not be an absolute contraindication to liver transplantation as these patients have reasonable long-term outcomes.

Simultaneous pancreas and kidney (SPK) retransplantation in prior SPK recipients.

INTRODUCTION: We have performed 113 renal and 28 isolated pancreas retransplants in our cohort of more than 1200 prior simultaneous pancreas and kidney (SPK) recipients. On the basis of these experiences, we began performing repeat SPK in prior SPK recipients (n = 9). METHODS: This retrospective review summarizes our experience with repeat SPK transplantation in prior SPK recipients. Mean age at retransplant was 39 yr; mean interval to retransplant was 7.8 yr. Thirty-three percent were pre-dialysis. Eighty-nine percent of patients underwent transplant nephrectomy (five during the repeat SPK and three prior to it), and 78% underwent transplant pancreatectomy (four during the repeat SPK and three prior to it). Enteric drainage was performed in all repeat SPKs. RESULTS: Median length of stay was 11 d. Perioperative complications included the following: renal artery thrombosis (1), pancreatic portal venous thrombosis (1), enteric leak (1), and hematoma (2). Overall pancreatic allograft survival was 78% at one yr and 67% at two yr. Overall renal allograft survival was 89% at one yr and 78% at two yr. Patient survival at one and three yr was 100%. CONCLUSIONS: Survival of repeat SPK allografts is acceptable despite the increased technical and immunologic demands of retransplantation. Graftectomy prior to or at the time of retransplantation is often necessary.

Alemtuzumab as compared to alternative contemporary induction regimens.

Between 1 January 2002 and 31 December 2007, our center performed 1687 adult renal transplants. A retrospective analysis was performed to compare outcomes between patients receiving alemtuzumab (n = 632) and those receiving either basiliximab (n = 690) or thymoglobulin (n = 125). Patients receiving alemtuzumab were younger (49 vs. 51 years, P = 0.02), had fewer HLA matches (1.7 vs. 2.0, P < 0.0001), were more likely to have a cytomegalovirus (CMV) donor(+)/recipient(-) transplant (22% vs. 17%, P = 0.03) and were less likely to receive a living donor allograft (32% vs. 37%, P = 0.04). Alemtuzumab recipients were less likely to receive tacrolimus (35% vs. 47%, P < 0.0001). The 1-, 3-, and 5-year cumulative incidence of antibody-mediated rejection (AMR) in alemtuzumab-treated patients was 19%, 24%, and 27%, vs. 11%, 15%, and 18% for the other group (P < 0.0001). The 1-, 3-, and 5-year allograft survival in the alemtuzumab group was 88%, 75%, and 67%, vs. 91%, 82%, and 74% for the other group (P < 0.0001). Patient survival was equivalent. Alemtuzumab was an independent risk factor for living donor allograft loss (HR 2.0, P = 0.004), opportunistic infections (HR 1.3, P = 0.01), CMV infections (HR 1.6, P = 0.001), and AMR (HR 1.5, P = 0.002). The significantly worse graft survival in the alemtuzumab cohort may be due to the increased rates of AMR and infectious complications.

Increase in proteinuria >200 mg/g after late rejection is associated with poor graft survival.

BACKGROUND: There is no information on the effects of proteinuria on outcomes following rejection. METHODS: We addressed this question in a retrospective study of 925 kidney transplant recipients between January 2003 and December 2007. Selection criteria were based on (i) biopsy proven diagnosis of a first episode of acute rejection, and (ii) available data on urine protein to creatinine (UPC) ratios at baseline (lowest serum creatinine before biopsy), time of biopsy and 1 month after biopsy. We examined the effects of a change in UPC (DeltaUPC = UPC 1 month after biopsy-baseline UPC) on outcomes. RESULTS: We identified 82 patients with both acute rejection and available data on proteinuria. Mean time (+/-SE) to acute rejection was 19 +/- 2.3 months, and patients were followed up for 38.7 +/- 2.6 months after transplant. Median DeltaUPC was 200 mg/g (95% confidence interval 0.00 to 0.300). Forty-two patients had a DeltaUPC > or =200 (high proteinuria group). Baseline characteristics were similar between high and low proteinuria groups except for more induction therapy with interleukin-2 receptor blockade in the former (71 vs. 47%, P = 0.04). Patient with DeltaUPC > or =200 had higher rates of graft loss (26 vs. 15%, P = 0.01) or combined graft loss or death (38 vs. 20%, P = 0.002 by log-rank). In univariate and multivariate Cox regression analyses, DeltaUPC > or =200 mg/g, sirolimus therapy 1 month after rejection and re-transplant status were significant factors associated with death-censored graft loss (hazard ratio (HR) 4.4, 14.9 and 6.2, P < or = 0.008) or combined graft loss or patient death (HR 3.8, 6.5 and 3.9, P < or = 0.03). Conclusions. An increase in proteinuria > or =200 mg/g after late acute rejection is associated with poor graft and patient outcomes. Clinical trials are needed to determine whether post-rejection anti-proteinuric strategies improve outcomes.

One-year serum albumin is an independent predictor of outcomes in kidney transplant recipients.

OBJECTIVE: This research study was conducted to investigate whether serum albumin levels predict allograft/patient outcomes in the new era of transplant medicine and immunology. METHODS: The association of 1-year post-transplant serum albumin, and patient and graft outcomes was retrospectively analyzed in 500 kidney transplant recipients between 1998 and 2005. Albumin was used as a categorical and a continuous variable in univariate and multivariate Cox regression and Kaplan-Meier survival analyses. RESULTS: The average (±SE) age at transplant was 47 ± 12 years. Patients were followed up for 63.4 ± 28 months after transplant. There were 56 graft losses and 38 patient deaths. In univariate analysis, the following variables were associated with the composite endpoint of patient death or allograft loss: 1-year serum albumin (hazard ratio [HR] = 0.52, P = .0009), 1-year serum albumin <4.0 g/dL (HR = 1.81, P = .02), 1-year serum creatinine (HR = 3.55, P < .00001), angiotensin converting enzyme inhibitors or angiotensin receptor blockers use (HR = 1.61, P = .03), a history of previous transplant (HR = 1.54, P = .04), months of dialysis before transplant (HR = 1.01, P = .00003), type of transplant (deceased donor HR = 1.64, P = .02), and acute rejection (HR = 1.52, P = .0000003). Of these, multivariable Cox regression analyses retained 1-year serum albumin (HR = 1.4, P < .0001), serum creatinine (HR = 2.7, P < .0001), and acute rejection (HR = 1.7, P = .02) as significant predictors of patient/graft loss. CONCLUSION: One-year serum albumin is an independent predictor of poor outcomes in the contemporary era of transplant medicine and immunosuppression. Further studies are needed to separate the role of this biomarker in inflammation and nutrition in kidney transplant recipients.

One thousand simultaneous pancreas-kidney transplants at a single center with 22-year follow-up.

OBJECTIVE: Simultaneous pancreas-kidney transplantation (SPK) is a procedure which frees the diabetic patient with end-stage nephropathy from dialysis and daily insulin injections. The purpose of this study is to report long-term outcomes of this procedure, and describe surgical and medical complications. METHODS: The analysis includes 1000 consecutive SPKs performed between 1985 and 2007. Bladder drainage was used in 390 patients and enteric drainage in 610 patients. In 362 patients, SPK transplantation was performed before initiation of dialysis. RESULTS: Patient survival at 1, 10, and 20 years is 97%, 80%, and 58%; kidney survival is 91%, 63%, and 38%; and pancreas survival is 88%, 63%, and 36%, respectively. There was no difference (P > 0.19) for patient, kidney, and pancreas survival between bladder and enteric drainage. Major surgical complications for bladder-drained patients were anastomotic leaks, urological complications, and infections. For enteric-drained patients, major surgical complications were infection, bleeding, and enzyme leak. Principal causes of death were myocardial infarction (n = 23), cerebrovascular accident (n = 18), and renal failure (n = 15). Graft failure for the kidney was due to acute rejection (n = 48), chronic rejection (n = 146), and death with a functioning graft (n = 99). Graft failure for the pancreas was caused by chronic graft loss (n = 44), thrombosis (n = 31), rejection (n = 80), and death with a functioning graft (n = 125). A total of 113 patients were retransplanted with either living related or unrelated donor kidneys (n = 64) or deceased donor kidneys (n = 42). Survival for retransplanted kidneys is 84% at 1 year and 68% at 5 years. Surviving bladder-drained patients underwent enteric conversion (>50%) for severe recalcitrant metabolic or urologic complications, most commonly enzyme leaks, hematuria, and recurrent urinary tract infection. CONCLUSIONS: Diabetic patients with end-stage renal failure have a poor prognosis without transplantation. Transplantation with SPK provides a marked extension of the patient's life and freedom from insulin injections. Enteric drainage is currently the surgical technique of choice. SPK transplantation should be considered the treatment of choice in this patient population.

Antibody-mediated rejection of the kidney after simultaneous pancreas-kidney transplantation.

The prevalence, risk factors, and outcome of antibody-mediated rejection (AMR) of the kidney after simultaneous pancreas-kidney transplantation are unknown. In 136 simultaneous pancreas-kidney recipients who were followed for an average of 3.1 yr, 21 episodes of AMR of the kidney allograft were identified. Eight episodes occurred early (

A prospective, randomized, double-blind, placebo-controlled multicenter trial comparing early (7 day) corticosteroid cessation versus long-term, low-dose corticosteroid therapy.

OBJECTIVE: To compare outcomes with early corticosteroid withdrawal (CSWD) and chronic low dose corticosteroid therapy (CCS). SUMMARY BACKGROUND DATA: Final, 5-year results from the first randomized, double-blind, placebo-controlled trial of early CSWD (at 7 days posttransplant) are presented. METHODS: Adult recipients of deceased and living donor kidney transplants without delayed graft function were randomized to receive prednisone (5 mg/d after 6 months posttransplant) or CSWD. Blinding was maintained for 5 years. This clinical trial is registered at www.clinicaltrials.gov (NCT00650468). RESULTS: Results in 386 patients CSWD (n = 191), CCS (n = 195) are presented (CSWD; CCS). No differences were observed at 5 years in the proportion of patients experiencing: primary end point (composite of death, graft loss, or moderate/severe acute rejection) (30/191 (15.7%); 28/195 (14.4%)), patient death (11/191(5.8%);13/195 (6.7%)), death-censored graft loss (11/191 (5.8%); 7/195(3.6%)), biopsy confirmed acute rejection (BCAR) (34/191 (17.8%); 21/195 (10.8%), P = 0.058), moderate/severe acute rejection (15/191 (7.9%); 12/195 (6.2%)). Kaplan Meier analyses of the primary end point and its components also showed no differences; but BCAR was higher with CSWD (P = 0.04). Increased BCAR episodes were primarily corticosteroid-sensitive Banff 1A rejections: the incidence of antibody-treated BCAR was similar between groups (11/191 (5.8%); 13/195 (6.7%)). No differences in renal function were observed at 5 years: mean serum creatinine (1.5 +/- 0.6; 1.5 +/- 0.7 mg/dL), or Cockroft Gault calculated creatinine clearance (58.6 +/- 19.7; 59.8 +/- 20.5 mL/min). CSWD was associated with improved serum triglycerides (evaluated by mean and median change from baseline) at all time points (except at 5 years measured by mean change). Weight change also demonstrated changes favoring CSWD (median change from baseline at 5 years: 5.1 vs. 7.7 kg, P = 0.05). New onset diabetes after transplant (NODAT) was similar with respect to proportions who required treatment (23/107 (21.5%)); 18/86 (20.9%); however, fewer CSWD patients required insulin for NODAT at 5 years (4/107 (3.7%)); 10/86 (11.6%), P = 0.049). Changes in HgA1c values (from baseline) were lower in CSWD patients at all time points except 4 years. CONCLUSIONS: Early CSWD, compared with CCS, is associated with an increase in BCAR primarily because of mild, Banff 1A, steroid-sensitive rejection, yet provides similar long-term renal allograft survival and function. CSWD provides improvements in cardiovascular risk factors (triglycerides, NODAT requiring insulin, weight gain). Tacrolimus/MMF/antibody induction therapy allows early CSWD with results comparable to long-term low dose (5 mg/d) prednisone therapy.

Bisphosphonates and bone fractures in long-term kidney transplant recipients.

BACKGROUND: There is little information on the role of bisphosphonates and bone mineral density (BMD) measurements for the follow-up and management of bone loss and fractures in long-term kidney transplant recipients. METHODS: To address this question, we retrospectively studied 554 patients who had two BMD measurements after the first year posttransplant and compared outcomes in patients treated, or not with bisphosphonates between the two BMD assessments. Kaplan-Meier survival and stepwise Cox regression analyses were performed to examine fracture-free survival rates and the risk-factors associated with fractures. RESULTS: The average time (+/-SE) between transplant and the first BMD was 1.2+/-0.05 years. The time interval between the two BMD measurements was 2.5+/-0.05 years. There were 239 and 315 patients in the no-bisphosphonate and bisphosphonate groups, respectively. Treatment was associated with significant preservation of bone loss at the femoral neck (HR 1.56, 95% CI 1.21-2.06, P=0.0007). However, there was no association between bone loss at the femoral neck and fractures regardless of bisphosphonate therapy. Stepwise Cox regression analyses showed that type-1 diabetes, baseline femoral neck T-score, interleukin-2 receptor blockade, and proteinuria (HR 2.02, 0.69, 0.4, 1.23 respectively, P<0.01), but not bisphosphonates, were associated with the risk of fracture. CONCLUSIONS: Bisphosphonates may prevent bone loss in long-term kidney transplant recipients. However, these data suggest a limited role for the initiation of therapy after the first posttransplant year to prevent fractures.

A systematic review of kidney transplantation from expanded criteria donors.

BACKGROUND: During the past few years, there has been renewed interest in the use of expanded criteria donors (ECD) for kidney transplantation to increase the numbers of deceased donor kidneys available. More kidney transplants would result in shorter waiting times and limit the morbidity and mortality associated with long-term dialysis therapy. STUDY DESIGN: Systematic review of the literature. SETTING & POPULATION: Kidney transplantation population. SELECTION CRITERIA FOR STUDIES: Studies were identified by using a comprehensive search through MEDLINE and EMBASE databases. Inclusion criteria were case series, cohort studies, and randomized controlled trials assessing kidney transplantation in adult recipients using ECDs. PREDICTOR: A special focus was given to studies comparing the evolution of kidney transplantation between standard criteria donors (defined as a donor who does not meet criteria for donation after cardiac death or ECD) and ECDs (defined as any brain-dead donor aged > 60 years or a donor aged > 50 years with 2 of the following conditions: history of hypertension, terminal serum creatinine level >or= 1.5 mg/dL, or death resulting from a cerebrovascular accident). OUTCOMES: Criteria used to define and select ECDs, practice patterns, long-term outcomes, early complications, and some patient issues, such as selection criteria and immunosuppressive management. RESULTS: ECD kidneys have worse long-term survival than standard criteria donor kidneys. The optimal ECD kidney for donation depends on adequate glomerular filtration rate and acceptable donor kidney histological characteristics, albeit the usefulness of biopsy is debated. LIMITATIONS: This review is based mainly on data from observational studies, and varying amounts of bias could be present. We did not attempt to quantitatively analyze the effect of ECD kidneys on kidney transplantation because of the huge heterogeneity found in study designs and definitions of ECD. CONCLUSIONS: Based on the available evidence, we conclude that patients younger than 40 years or scheduled for kidney retransplantation should not receive an ECD kidney. Patients 40 years or older, especially with diabetic nephropathy or nondiabetic disease, but a long expected waiting time for kidney transplantation, show better survival receiving an ECD kidney than remaining on dialysis therapy.

Two years postconversion from a prograf-based regimen to a once-daily tacrolimus extended-release formulation in stable kidney transplant recipients.

Tacrolimus extended-release (XL) is a once-daily formulation recently developed to reduce the frequency of dosing for patients currently using the twice-a-day formulation of tacrolimus (TAC). As reported previously, 67 kidney transplant recipients were safely converted (1:1 mg basis, total daily dose) from TAC twice-a-day to XL once-daily in the morning and were maintained on an am dosing regimen of XL using the same therapeutic monitoring and patient care techniques currently employed with TAC. The 2-year postconversion patient (100%) and graft (98.5%) survival, incidence of biopsy-confirmed acute rejection (6.0%), incidence of multiple rejections (1.5%), and safety profile (posttransplant diabetes, hyperlipidemia, hypertension, infections, renal dysfunction, hepatic dysfunction, and malignancies) were consistent with or more favorable than those previously reported for TAC twice-a-day.

Improvement in 3-month patient-reported gastrointestinal symptoms after conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in renal transplant patients.

BACKGROUND: The benefit of conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) in terms of gastrointestinal symptom burden has been evaluated previously using patient-reported outcomes. However, data are lacking concerning the sustained effect of conversion over time, and the potential impact of concomitant calcineurin inhibitor. METHODS: In this 3-month, prospective, multicenter, longitudinal, open-label trial, MMF-treated renal transplant patients with gastrointestinal symptoms receiving cyclosporine or tacrolimus were converted to equimolar doses of EC-MPS. Change in gastrointestinal symptom burden was evaluated using a validated Gastrointestinal Symptom Rating Scale (GSRS). RESULTS: A significant improvement in GSRS score was observed from baseline (2.61, 95% CI 2.54-2.68) to month 1 (1.87, 95% CI 1.81-1.93) after conversion to EC-MPS and was sustained to month 3 (1.81, 95% CI 1.74-188; both P<0.0001 versus baseline). The mean change in overall GSRS score from baseline to month 1 was -0.74 overall (cyclosporine: -0.73 and tacrolimus: -0.74; all P<0.0001 versus baseline), with a slight further improvement (-0.79) at month 3 (cyclosporine: -0.82 and tacrolimus: -0.78; all P<0.0001 versus baseline). A significant improvement in GSRS subscale scores was also observed in the total population regardless of calcineurin inhibitor at month 1, sustained to month 3 (all P<0.0001 versus baseline). The improvement in GSRS score postconversion was similar in African-American and non-African-American patients, and in diabetic and nondiabetic patients. CONCLUSIONS: This exploratory study in 728 patients demonstrates that following conversion from MMF to EC-MPS, regardless of concomitant calcineurin inhibitor, GSRS is improved and sustained over 3 months.

Alemtuzumab induction and recurrence of glomerular disease after kidney transplantation.

BACKGROUND: An increase in the incidence of autoimmune diseases has been described in patients receiving alemtuzumab. METHODS: To determine whether induction with alemtuzumab increases recurrence of glomerular disease, we performed a retrospective study in 443 patients with biopsy-proven glomerular diseases undergoing kidney transplantation. Patients receiving alemtuzumab (n=161) were compared with those receiving interleukin (IL)-2-receptor antagonists (n=217) or antithymocyte globulin (n=64). RESULTS: Biopsy-proven glomerular disease recurrence was similar in patients induced with alemtuzumab or IL-2 receptor antagonists. Patients receiving antithymocyte antibody had a lower recurrence rate than patients treated with other induction agents, with borderline significance (hazard ratio [HR] 0.13, 95% confidence interval [95% CI] 0.02-0.98, P=0.047). Patients with systemic lupus treated with alemtuzumab had a similar re-emergence of autoreactive antibodies to patients treated with other agents. Recurrent disease increased the risk of allograft failure (HR 2.36, 95% CI 1.28-4.32, P=0.0056). The development of acute rejection and the use of deceased (vs. living) donor kidneys were also significant factors influencing graft survival. A greater risk of mortality was detected in those patients with recurrent glomerular disease (HR 3.76, 95% CI 1.37-10.35, P=0.01), whereas increased age at transplantation (HR 1.05) and the use of deceased (vs. living) donor kidneys (HR 3.20) also increased mortality. No specific induction agent significantly affected graft loss or mortality when using adjusted or unadjusted hazard ratios. CONCLUSIONS: In this retrospective analysis, induction with alemtuzumab did not increase the rate of re-emergence of autoantibodies or biopsy-proven recurrence of glomerular disease. A slight reduction in the incidence of recurrence was observed in patients treated with thymoglobulin, yet this observation can only be validated in a prospective randomized trial.

A 30-year analysis of colorectal adenocarcinoma in transplant recipients and proposal for altered screening.

PURPOSE: The risk of malignancy after solid-organ transplantation is well documented. However, the incidence and specific risk for colorectal adenocarcinoma, although previously proposed, has been difficult to calculate. We reviewed the University of Wisconsin transplant database for all cases of colorectal adenocarcinoma to assess the risk of this malignancy, as well as the need for improved screening in this population. METHODS: The transplant database was queried using diagnosis codes for colorectal adenocarcinoma to configure a list of eligible patients. Exclusion criteria included: age less than 18 years at the time of transplant, diagnosis of colorectal cancer or patient death less than 12 months posttransplant, and pretransplant history of colorectal cancer or proctocolectomy. Statistical analysis determined overall incidence, age-specific incidence, and survival for this population. RESULTS: A total of 5,603 kidney, liver, or combination transplants were eligible for analysis from 1966 through 2004. The mean follow-up was 9.3 years. We identified 40 cases of colorectal adenocarcinoma. Twenty-five of these cases (62%) occurred in kidney transplant recipients, 13 after liver transplant, and two after kidney-pancreas combination. Twenty-seven patients (68%) diagnosed with cancer have died, 12 of metastatic disease. The median survival postcancer diagnosis was 2.3 years. These results were compared to the National Cancer Institute Survival, Epidemiology, and End Results (SEER) database for colon and rectal cancer. The current age-adjusted annual incidence based on year 2000 census data is 0.053% (52.9/100,000), and the extrapolated 10-year incidence is 0.27%. The 10-year incidence in the transplanted cohort is 0.71% (incidence ratio = 2.6). The 5-year survival postcancer diagnosis is 63.5% in the general population (SEER), vs. 30.7% in the transplant cohort. The SEER median age at diagnosis of colorectal adenocarcinoma is 72.0 years. Of the transplant recipients who developed cancer, the median age at diagnosis was 58.7 years (32.4 to 78.2), and 11 patients (27%) were diagnosed at or before age 50. In the U.S. population, the annual incidence of colorectal adenocarcinoma below the age of 50 is 0.0055% (5.52/100,000) and the 10-year extrapolated incidence is 0.11%. The 10-year incidence in the under-50 transplant cohort is 0.33% (incidence ratio = 3.0). In this under-50 cohort, median time from transplant to cancer diagnosis was 7.8 years. CONCLUSION: The incidence of and 5-year survival after diagnosis of colorectal adenocarcinoma in transplant recipients is markedly different than the general population. Patients are often diagnosed at a younger age. With current screening guidelines, over 25% of at-risk patients would not be screened. We propose modifying these guidelines to allow earlier detection of colorectal cancer in this population.