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.

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.

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 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.

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.

Association of cytomegalovirus disease and acute rejection with graft loss in kidney transplantation.

BACKGROUND: Cytomegalovirus (CMV) and acute rejection (AR) alone have been associated with an increased risk of graft loss in kidney transplantation. However, little is known about their association with graft loss when both affect the transplant recipient. METHODS: By using the dynamic time-varying covariate approach to the Cox-proportional hazards model, we retrospectively analyzed the strength of association of AR and CMV disease on graft loss in a single-center kidney and simultaneous pancreas-kidney transplant population. RESULTS: Between January 1990 and December 2000, 2,740 kidney and simultaneous pancreas-kidney transplants were performed at the authors' center. The overall 5-year incidence of biopsy-proven AR and CMV disease was 45.8% (n=1,254) and 15.3% (n=420), respectively. The risk ratio (RR) for graft loss was increased by the presence of AR (RR=3.7; P<0.0001), CMV disease (RR=1.9; P=0.0007), AR following CMV disease (RR=6.6; P<0.0001), and CMV disease following AR (RR=3.3; P<0.0001). In patients with AR and CMV disease the average time until AR occurred was longer (441 days) when AR followed CMV disease in comparison with when AR preceded CMV disease (47 days). After adjusting for time-dependent risk of AR for kidney graft loss, the order of AR and CMV disease had no association with graft loss (RR=1.2; P=0.5055). CONCLUSIONS: These results demonstrate the strength of AR and CMV disease as prognosticators of impeding kidney graft loss in transplant recipients. Although AR usually precedes CMV disease, the order of AR and CMV disease has no impact on kidney graft loss in kidney and simultaneous pancreas-kidney transplant recipients.

Underutilization of pancreas donors.

BACKGROUND: Transplantation of the pancreas has become the treatment of choice for selected patients with type 1 diabetes mellitus. With the current shortage of cadaver donors and the increasing number of diabetic patients on the transplant waiting list, there is a critical need to optimally use all available pancreas grafts for transplantation. We have therefore explored the use of traditionally "less-than-ideal" pancreas donors, including pediatric (4-10 years), older (>or=45 years), obese (weight >or=200 lb), and non-heart-beating donors and donors with an elevated amylase (75% greater than normal values). METHODS: A total of 620 primary simultaneous pancreas-kidney transplantations were performed at our center. We analyzed the ratio of livers to pancreata transplanted at our center and compared this to the United Network for Organ Sharing database. Using univariate and multivariate analyses, we then assessed the impact of these less-than-ideal donors on patient survival, graft survival, and postsurgical complications after simultaneous pancreas-kidney transplantation. RESULTS: A substantial nationwide underutilization of pancreata from donor procurements is demonstrated in the United Network for Organ Sharing database. By using these less-than-ideal donors, the ratio of liver to pancreata procured can be reduced to 1.25:1. Graft survival was not significantly different in patients receiving transplants from obese, non-heart-beating, pediatric, or hyperamylasemic donors compared with grafts from ideal donors. However, grafts from donors 45 years of age or older had significantly lower 1- and 5-year graft survival rates (76% and 65% vs. 90% and 80%, P=0.006). CONCLUSIONS: This study demonstrates that utilization of pancreas grafts from selected, less-than-ideal donors results in good overall outcomes and could potentially expand the organ donor pool.

Chronic allograft nephropathy uniformly affects recipients of cadaveric, nonidentical living-related, and living-unrelated grafts.

BACKGROUND: Chronic allograft nephropathy (CAN) remains a major barrier to long-term allograft survival. The authors retrospectively compared the development of CAN in recipients of cadaveric (CAD), living-related donor (LRD), and living-unrelated donor (LURD) transplants at their center. METHODS: The authors retrospectively examined the impact of various factors on the incidence of CAN using univariate and multivariate proportional hazards analysis in a single-center kidney transplant population. RESULTS: Between 1 January 1990 and 31 May 2000, 2,140 kidney-alone transplants were performed at the authors' center. The overall 5-year incidence of biopsy-proven CAN was 12.2% (n=203). Risk factors for CAN included the number of transplants (P=0.0001), acute rejection (P=0.0001), panel reactive antibody (P=0.0001), discharge creatinine (P=0.0001), 1-year creatinine (P=0.0015), delayed graft function (P=0.007), total human leukocyte antigen (HLA)-B and -DR mismatches (P=0.0005), recipient age (P=0.003), black donor race (P=0.001), black recipient race (0.0457), donor age (P=0.0053), cold storage time (P=0.019), and cytomegalovirus infections (P=0.002). Interestingly, although the LRD HLA-identical recipients had a significantly lower incidence of CAN (P=0.0015), the incidence of CAN in CAD and HLA-nonidentical LRD recipients did not differ. Graft survival was significantly worse in CAD recipients compared with all other groups (P<0.001). CONCLUSIONS: These results demonstrate the importance of immunologic and nonimmunologic factors on the development of CAN. The disparities in overall graft survival, despite the similarities in CAN rates, suggests that other factors, in addition to CAN, influence the increase in graft loss in CAD transplant recipients.

Reassessing the impact of cytomegalovirus infection in kidney and kidney-pancreas transplantation.

New antiviral agents and practice guidelines have been implemented to address cytomegalovirus (CMV) infection in organ transplantation. We hypothesized that such measures would reduce rates of symptomatic CMV infection, CMV disease, and CMV seroconversion and associated complications in renal transplant and simultaneous pancreas-kidney transplant recipients. We analyzed the impact of CMV in 1,424 renal transplant and simultaneous pancreas-kidney transplant recipients, transplanted at our center between January 1, 1994 and June 30, 1999. Most patients received quadruple sequential immunosuppression with high-dose acyclovir (800 mg four times daily) for 12 weeks as prophylaxis. High-risk patients (donor CMV-positive/recipient CMV-negative) received ganciclovir (500 to 1,000 mg three times daily) beginning in 1998, again for 12 weeks. One hundred and one renal transplant (9.0%) and 40 simultaneous pancreas-kidney transplant (13.4%) recipients experienced symptomatic CMV infection or CMV disease. Donor CMV-positive/recipient CMV-negative patients had the greatest rates of CMV infection or CMV disease (25.2%; P = 0.0001 versus all other categories). The impact of CMV on outcomes was evaluated in a proportional hazards model. Symptomatic CMV infection or CMV disease increased the risk for subsequent rejection (relative risk, 2.11; P = 0.003) and non-CMV infection (relative risk, 2.24; P = 0.001). To determine if the effects of ganciclovir were masked by pre-1998 data, CMV infection and CMV disease rates for ganciclovir-treated patients (n = 62) were censored at 1 year and compared with acyclovir-treated patients (n = 287). Ganciclovir was associated with trends toward lower rates of infection and disease. It also delayed the time to infection or disease. Serologic testing in high-risk patients also showed late seroconversion, with 20% of patients seroconverting by 6 months, 12 weeks after the prophylaxis period. These data suggest that despite better prophylaxis strategies, CMV remains an important pathogen in renal transplant and simultaneous pancreas-kidney transplant recipients. This finding may require reassessment of prophylaxis strategies and the development of alternative or novel anti-CMV regimens.

Outcomes in kidney transplantation.

It is estimated that there are greater than 100000 kidney transplant recipients with a functioning graft in the United States. Recent advances in immunosuppression have improved short-term graft survival rates and decreased early mortality by decreasing the incidence and therapy for acute rejection episodes. For those accepted on the waiting list, transplant prolongs patient survival compared with remaining on dialysis. During the 1990s, 3 new immunosuppressive drugs were introduced in clinical kidney transplantation. All were approved for use by the Food and Drug Administration after large, controlled, randomized trials. Mycophenolate mofetil (MMF), when combined with cyclosporine (CSA) and prednisone, lowered acute rejection rates by nearly 50% compared with control. Tacrolimus compared with CSA also significantly reduced acute rejection rates in kidney transplant recipients, but was associated with a significant increase in posttransplant diabetes mellitus (PTDM) in the early trials. When evaluated in combination with MMF, the incidence of PTDM was much lower. At the end of the decade, sirolimus was shown in several randomized trials to lower acute rejection rates and is believed to be less nephrotoxic compared with calcineurin inhibitors. All of the randomized trials were not statistically powered to assess long-term superiority. Registry analyses have been performed that appear to show some long-term benefit of immunosuppressive therapy with MMF. Other outcome assessments in kidney transplant recipients include risk factors for chronic allograft nephropathy, hypertension, hyperlipidemia, and bone disease. Although there are few randomized trials, understanding of the significance of these common complications has progressed and strategies for therapy and intervention have been developed. This article focuses on the randomized trials of immunosuppressive therapy and complications associated with use of these drugs. In addition, we review the current management and intervention for the comorbidities associated with the long-term clinical management of the kidney transplant recipient.

Determinants of quality of life changes among long-term cardiac transplant survivors: results from longitudinal data.

BACKGROUND: Cross-sectional analyses have identified significant associations between quality of life (QOL), and comorbidities and adverse effects in cardiac transplant recipients. However, little is known about factors that influence changes in QOL over time. This study examines both cross-sectional and longitudinal data from long-term survivors to identify factors that affect differences in QOL among recipients and individual changes in QOL during a 1-year period. METHODS: Self-selected enrollees completed questionnaires, including QOL scales, at 3-month intervals. Repeated measures multiple regression analysis was used to examine the association between the QOL scales and comorbidities, adverse effects, and compliance measures, controlling for other factors. RESULTS: We included 569 participants in the analysis, with a mean time since transplantation of 8.6 years. Cross-sectional results showed that the number of comorbidities, treatment non-compliance, and several adverse effects were associated with low QOL. In longitudinal results, waiting to take medications and taking less medication because of lifestyle restrictions were associated with decreases in QOL over time. Hair loss, changes in face shape, and decreased sexual interest or ability also had the largest adverse effects on changes in QOL. CONCLUSIONS: These findings provide new opportunities for interventions to address factors related to decreases in QOL. Clinicians should actively solicit information about compliance with medication regimens. In addition, information about the adverse effects of medications should be considered when making therapeutic decisions.