Utility of mammography for chronic kidney disease patients undergoing kidney transplant evaluation.

UNLABELLED: Transplant centers typically require screening mammography (MMG) for women ≥40 during evaluation. American Cancer Society recommends starting annual MMG at 40, while USPSTF recommends biennial MMG at 50. We sought to determine the effect of age and other breast malignancy risk factors on screening MMG in the pre-transplant renal failure population undergoing transplant evaluation. METHODS: We retrospectively examined women ≥40 undergoing kidney transplant evaluation from 2006 to 2012 (n = 541). RESULTS: Patients aged 40.0-49.9 and ≥50 had similar rates of breast biopsy and breast malignancy. African Americans underwent a higher rate of biopsies (OR 2.391, 95%CI 1.111-5.019, p = 0.026), with a lower rate of biopsy in those already on dialysis at presentation (OR 0.434, 95%CI 0.212-0.888, p = 0.022). Higher breast density (>50% fibroglandular tissue) increased both rate of biopsy (OR 2.876, 95%CI 1.377-6.010, p = 0.005) and malignancy (OR 5.061, 95%CI 1.012-25.315, p = 0.048). CONCLUSIONS: As we found no independent differences in biopsy or malignancy between age groups, it is reasonable for transplant centers to use the same evaluation MMG screening policy for all women ≥40. However, as malignancy risk increased with higher breast density, a lower threshold for additional workup may be warranted in patients with dense breasts or an indeterminate lesion on MMG.

Enhancing kidney function with thrombolytic therapy following donation after cardiac death: a multicenter quasi-blinded prospective randomized trial.

Kidneys from donors after cardiac death (DCD) are at risk for inferior outcomes, possibly due to microthrombi and additional warm ischemia. We describe an organ procurement organization-wide trial utilizing thrombolytic tissue plasminogen activator (tPA) during machine pulsatile perfusion (MPP). A kidney from each recovered kidney pair was prospectively randomized to receive tPA (50 mg Alteplase) or no tPA (control) in the MPP perfusate. From 2011 to 2013, 24 kidneys were placed with enrolled recipients from 19 DCD kidney donors. There were no significant differences for absolute values of flow or resistance while undergoing MPP between the groups, nor rates of achieving discrete flow and resistance targets. While there was a trend toward lower creatinine and higher glomerular filtration rates in the tPA group at 3, 6, 9, and 12 months, these differences were not significant. Delayed graft function (DGF) rates were 41.7% in the tPA group vs. 58.4% in the control group (OR 0.51, 95%CI 0.10-2.59, p = 0.68). Death-censored graft survival was similar between the groups. In this pilot study, encouraging trends are seen in kidney allograft function independent of MPP parameters following DCD kidney transplantation for those kidneys receiving thrombolytic tPA and MPP, compared with standard MPP.

Indications for combined liver and kidney transplantation: propositions after a 23-yr experience.

The frequency of combined liver and kidney transplants (CLKT) persists despite the pronounced scarcity of organs. In this review, we sought to ascertain any factors that would reduce the use of these limited commodities. Seventy-five adult CLKT were performed over a 23-yr period at our center, 29 (39%) of which occurred during the Model for End-stage Liver Disease (MELD) era. Overall, patient survival rates were 82%, 73%, and 62% at one, three, and five yr, respectively. There was no difference in patient survival based either on pre-transplant hemodialysis status or by glomerular filtration rate (GFR) at the time of transplant. Patients undergoing a second CLKT or a liver retransplantation at the time of CLKT had a survival rate of 30% at three months. In the MELD era, patient survival was unchanged (p = NS) despite an older recipient population (p = 0.0029) and a greater number of hepatitis C patients (p = 0.0428). In summary, patients requiring liver retransplantation with concomitant renal failure should be denied CLKT. Renal allografts may also be spared by implementing strict criteria for renal organ allocation (GFR < 30 mL/min at the time of evaluation) and considering the elimination of preemptive kidney transplantation in CLKT.

Acute kidney injury following liver transplantation: definition and outcome.

The incidence of acute kidney injury (AKI) has been reported to vary between 17% and 95% post-orthotopic liver transplantation. This variability may be related to the absence of a uniform definition of AKI in this setting. The purpose of this study was to identify the degree of AKI that is associated with long-term adverse outcome. Furthermore, to determine the best definition (for use in future studies) of AKI not requiring dialysis in post-liver transplant patients, we retrospectively reviewed the effect of 3 definitions of AKI post-orthotopic liver transplantation on renal and patient outcome between 1997 and 2005. We compared patients with AKI to a control group without AKI by each definition. AKI was defined in 3 groups as an acute rise in serum creatinine, from the pretransplant baseline, of >0.5 mg/dL, >1.0 mg/dL, or >50% above baseline to a value above 2 mg/dL. In all groups, the glomerular filtration rate was significantly lower at both 1 and 2 years post-transplant. Patient survival was worse in all groups. Graft survival was worse in all groups. The incidence of AKI was highest in the group with a rise in creatinine of >0.5 mg/dL (78%) and lowest in patients with a rise in creatinine of >50% above 2.0 mg/dL (14%). Even mild AKI, defined as a rise in serum creatinine of >0.5 mg/dL, was associated with reduced patient and graft survival. However, in comparison with the other definitions, the definition of AKI with the greatest impact on patient's outcome post-liver transplant was a rise in serum creatinine of >50% above baseline to >2 mg/dL.

Twenty years' follow-up of portal vein conduits in liver transplantation.

Portal vein problems remain a formidable challenge in liver transplantation. In select situations, a portal vein conduit can provide a solution. No long-term results have been reported. This study was designed to assess the impact of portal vein conduits on graft survival after liver transplantation and the safety of portal vein conduits and to establish the long-term results (up to 20 years) of portal vein conduits. Data from 2370 adult liver transplants were prospectively collected into a computerized research database and analyzed. All portal vein conduits were constructed from the donor iliac vein obtained at the liver retrieval. Portal vein conduits were required in 35 (1.5%) first transplants. The long-term (up to 20 years of follow-up) graft survival after liver transplantation using portal vein conduits was excellent and comparable to that of the control group. The graft survival was 65% with the conduit versus 66% without the conduit at 5 years of follow-up, 58% versus 51% at 10 years, and 48% versus 35% at 15 years. There was a higher rate (8.6% versus 1.4%) of portal vein thrombosis after the portal vein conduit, and the majority occurred in the first 3 months after transplantation. For the same time period, there was no statistically significant difference in graft survival or patient survival for the retransplants with and without portal vein conduits. There was no statistically significant difference in graft survival or patient survival for the transplants with portal vein conduits and with portal vein thrombendvenectomy. In conclusion, portal vein conduits can be used safely for liver transplantation with no negative impact on long-term graft survival or patient survival. Despite the higher rate of portal vein thrombosis in the immediate postoperative period, excellent long-term results can be obtained.

Impact of sirolimus on the recurrence of hepatocellular carcinoma after liver transplantation.

Tumor recurrence after liver transplantation for hepatocellular carcinoma is associated with a poor prognosis. Because immunosuppression is a well-known risk factor for tumor growth, it is surprising that its possible role in the outcome of liver transplantation has been poorly evaluated. We performed a case-control review of prospectively collected data and compared 2 groups of patients according to the type of immunosuppression after liver transplantation for hepatocellular carcinoma at a single center. One hundred six patients received tacrolimus and mycophenolate mofetil, and 121 received sirolimus. Patients in the sirolimus group had significantly higher recurrence-free survival rates than patients in the tacrolimus group (P = 0.0003). The sirolimus group also had significantly higher patient survival rates than the tacrolimus group at 1 year (94% versus 79%), 3 years (85% versus 66%), and 5 years (80% versus 59%; P = 0.001). Sirolimus was well tolerated, and the patients in this study did not have the increase in surgical complications noted by other investigators. Leukopenia was the most common side effect, but it typically resolved with dose reduction. Dyslipidemia and mouth ulcers were common but were easily controlled. In summary, the data suggest a beneficial effect of sirolimus immunosuppression on recurrence-free survival, which translates into patient survival benefits.

Risk Factors for Abnormal Cervical Cytology in Women Undergoing Kidney Transplant Evaluation.

OBJECTIVES: Cervical cytology screening has been successful in reducing deaths from cervical cancer. We sought to determine risk factors for abnormal Pap test results in women undergoing kidney transplant evaluation. MATERILAS AND METHODS: We retrospectively examined women undergoing kidney transplant evaluations from 2008 to 2011. Patients were stratified based on normal cytology and atypical/malignant cytology. RESULTS: Of 404 patients, 293 patients (72.5%) had normal cytologic findings, whereas 111 (27.5%) had abnormal findings. On univariate logistic regression analyses, patients who had chronic kidney disease with an autoimmune cause (odds ratio = 2.71 [95% confidence interval, 1.41-5.19]; P = .003), previous renal transplants (odds ratio = 2.64 [95% confidence interval, 1.20-5.82], P = .016), or age ≤ 50 years (odds ratio = 1.68 [95% confidence interval, 1.08-2.61], P = .022) were more likely to have abnormal findings. Patients with normal and abnormal findings had similar rates of dialysis use. On multivariate logistic regression, patients who had chronic kidney disease with autoimmune causes (odds ratio = 2.48 [95% confidence interval, 1.26-4.88]; P = .008) and who had previous renal transplants (odds ratio = 2.67 [95% confidence interval, 1.20-5.95]; P = .017) were more likely to have abnormal findings. CONCLUSIONS: Previous kidney transplant, autoimmune disease, and age ≤ 50 years were associated with abnormalities on cervical cancer screening in our female group of patients. Patients with these characteristics may benefit more from routine cervical cancer screening than other patients evaluated for kidney transplant.

Transmission of rabies virus from an organ donor to four transplant recipients.

BACKGROUND: In 2004, four recipients of kidneys, a liver, and an arterial segment from a common organ donor died of encephalitis of an unknown cause. METHODS: We reviewed the medical records of the organ donor and the recipients. Blood, cerebrospinal fluid, and tissues from the recipients were tested with a variety of assays and pathological stains for numerous causes of encephalitis. Samples from the recipients were also inoculated into mice. RESULTS: The organ donor had been healthy before having a subarachnoid hemorrhage that led to his death. Encephalitis developed in all four recipients within 30 days after transplantation and was accompanied by rapid neurologic deterioration characterized by agitated delirium, seizures, respiratory failure, and coma. They died an average of 13 days after the onset of neurologic symptoms. Mice inoculated with samples from the affected patients became ill seven to eight days later, and electron microscopy of central nervous system (CNS) tissue demonstrated rhabdovirus particles. Rabies-specific immunohistochemical and direct fluorescence antibody staining demonstrated rabies virus in multiple tissues from all recipients. Cytoplasmic inclusions consistent with Negri bodies were seen in CNS tissue from all recipients. Antibodies against rabies virus were present in three of the four recipients and the donor. The donor had told others of being bitten by a bat. CONCLUSIONS: This report documenting the transmission of rabies virus from an organ donor to multiple recipients underscores the challenges of preventing and detecting transmission of unusual pathogens through transplantation.

Twenty years of follow-up of aortohepatic conduits in liver transplantation.

Arterial problems remain a formidable challenge in liver transplantation. In many situations, an aortohepatic conduit can provide a solution. No long-term results (over 5 years) have been reported. This study was designed to assess the impact of aortohepatic conduits on graft survival after liver transplantation and the safety of aortohepatic conduits and to establish the long-term results (up to 20 years) of aortohepatic conduits. Data from 2346 adult liver transplants were prospectively collected into the computerized database and analyzed. In the majority of cases, arterial conduits were constructed from the donor iliac artery obtained at the liver retrieval. Aortohepatic conduits were required in 149 (6.4%) first transplants. The long-term graft survival after liver transplantation using aortohepatic conduits was excellent and comparable to that of the control group. The graft survival was 59% with the conduit versus 67% without the conduit at 5 years of follow-up, 50% versus 52% at 10 years, and 33% versus 35% at 15 years. With up to 20 years of follow-up, there was no statistically significant difference in graft survival, patient survival, hepatic artery complications, or biliary complications. For the same time period, there was no statistically significant difference in graft survival or patient survival for the retransplants with and without aortohepatic conduits. In conclusion, in experienced hands, aortohepatic conduits can be used safely for liver transplantation with no negative impact on long-term graft survival, patient survival, hepatic artery complications, or biliary complications. Excellent long-term results can be obtained.

Late acute rejection after liver transplantation impacts patient survival.

Hepatic allograft rejection still remains an important problem following liver transplantation. Early acute rejection, occurring within three months of transplant, is a common event and usually of lesser significance with respect to prognosis than other non-immune-related post-transplant morbidities. However, little is known about late acute rejection (LAR) including factors affecting its occurrence and long-term outcome. In this study, we analyzed LAR including the incidence, clinical risk factors, patient survival, and graft survival. LAR was defined as acute cellular rejection later than six months after liver transplant. Adult patients who had a minimum of 24 months of graft survival were included in this study. A total of 1604 case records of consecutive adult patients (over age 18 yr) who underwent liver transplant between 1985 and 2003 were reviewed. Of the 1604 patients, 305 (19.0%) developed LAR. Patients with primary diagnoses of autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis had higher incidences of LAR, while patients with metabolic disease and retransplant had lower incidence of LAR (p = 0.0024). The LAR group had more female and younger recipients than the no LAR group (p = 0.0026, p = 0.0131, respectively). Patient survival as well as graft survival were significantly lower in the LAR group (p = 0.0083, p = 0.0075, respectively). PTLD was the only significant independent predictor of late rejection. The careful management and treatment of PTLD, especially immunosuppressive management, is important to prevent LAR, which is related to poorer patient survival.

Advantages of time-resolved contrast-enhanced 4D MR angiography in splenic arterial steal syndrome.

Splenic artery steal syndrome (SASS) is a severe complication affecting up to 10% of orthotopic liver transplant (OLT) patients. In this case report, we present a 35-year-old male with OLT secondary to liver failure due to hemochromatosis, who developed SASS. We describe potential application of different imaging techniques for diagnosis of SASS with focus on the value of time-resolved contrast enhanced 4D magnetic resonance angiography (MRA).

The Utility of Screening Colonoscopy During Kidney Transplant Evaluation.

OBJECTIVES: Transplant centers often recommend, but not necessarily require, screening colonoscopies for people over 50 years of age in accordance with the US Preventative Services Task Force guidelines for the general population. We sought to identify risk factors affecting colonoscopy results in renal failure patients undergoing kidney transplant evaluation. MATERIALS AND METHODS: We retrospectively examined patients undergoing kidney transplant evaluation from 2009 to 2012 (n = 469 patients). Comparisons were made between colonoscopy reports categorized as normal (no finding or hyperplastic polyp) or abnormal (adenomatous polyp or carcinoma). RESULTS: Of 469 patients who met the study criteria, 303 (64.6%) had normal colonoscopies and 166 (35.4%) had abnormal colonoscopies. Logistic regression analysis showed that male sex (odds ratio = 2.09; 95% confidence interval, 1.37-3.20; P = .001) and increasing age (odds ratio = 1.04; 95% confidence interval, 1.01-1.08; P = .019) were more likely to correspond to abnormal findings. Those with dialysis vintage (length of time on dialysis) up to 3 years (odds ratio = 2.10; 95% confidence interval, 1.09-4.06; P = .027) and hypertension as the cause of renal failure (odds ratio = 1.79; 95% confidence interval, 1.05-2.87; P = .002) had more abnormal findings. No differences in length of evaluation, rate of being listed for transplant, and rate of transplant were shown. CONCLUSIONS: The overall rate of adenomatous findings on colonoscopy was higher among patients with pretransplant end-stage renal disease than in the general population, as shown in other studies. Age, sex, dialysis vintage up to 3 years, and hypertensive renal failure were associated with adenomatous polyps of the colon in this study population. Because adenomatous polyp rates are high in patients with chronic kidney disease who are undergoing transplant evaluation and colonoscopic findings do not appear to delay transplant evaluations or listing rates, screening colonoscopies should be encouraged.

Liver and kidney transplantation for polycystic liver and kidney-renal function and outcome.

BACKGROUND: Polycystic liver disease (PLD) is a rare disorder frequently associated with polycystic kidney disease (PKD). Transplantation is a treatment option for these patients. Because of preservation of hepatic function in these patients, liver transplantation is not routinely utilized. We report a large series of PLD patients and their outcomes following liver and kidney transplantation. METHODS: Fourteen patients underwent orthotopic liver transplantation (OLTx) for PLD between 1987 and 2003. Twelve patients had PKD combined with PLD. Nine patients received only liver transplantation. Five patients had combined liver and kidney transplantation. Thirteen patients (93%) survived for at least one year following liver transplantation. Two out of eight patients who received solitary liver transplantation later required kidney transplantation. RESULTS: Pretransplant glomerular filtration rate (GFR) in patients with PKD was 75.8+/-25.4 ml/min/1.73 m. One year later, GFR was 37.2+/-8.3 ml/min/1.73 m. Kaplan-Meier analysis showed that one- and two-year graft survival for combined liver and kidney transplantation was 80% (n=5), whereas graft survival for solitary liver transplantation was 100% (n=9). Mean survival of patients who had combined liver and kidney transplantation was 46.7+/-54.2 months (n=5), whereas the mean survival for solitary liver transplant patients was 80.4+/-68.6 months (n=9) (P=0.36). CONCLUSION: Transplantation is an excellent option for PLD with dramatic improvement in quality of life and acceptable morbidity. For combined liver and kidney transplantation one- and two-year patient survival rates were similar to combined transplantation for other indications. For patients with acceptable renal function at time of transplantation, solitary liver transplantation has an excellent outcome.

Rabies encephalomyelitis: clinical, neuroradiological, and pathological findings in 4 transplant recipients.

BACKGROUND: Three patients received solid organ transplants from a common donor and were subsequently discharged from the hospital following an uneventful hospital course. Within 30 days, all 3 organ recipients returned to the hospital with varying symptoms that progressed to rapid neurological deterioration, coma, and death. OBJECTIVE: To describe the clinical, neuroradiological, and pathological findings of rabies virus infection in organ transplant recipients infected from a common donor. DESIGN: Case series involving a common donor and 3 organ recipients ascertained through review of clinical course and autopsy findings. A fourth case was determined by review of pending autopsy cases in which death occurred within the same time interval. Portions of postmortem central nervous system and organ tissues were frozen and formalin-fixed. Fluids and tissues were also collected for cultures, serology, and molecular studies. Postmortem fluids and tissues and antemortem fluids and tissues from all 4 transplant recipients and serum and banked lymphocyte or spleen cells from the donors were sent to the Centers for Disease Control and Prevention for further evaluation. SETTING: Transplant unit of an urban teaching hospital. RESULTS: Antemortem cerebrospinal fluid analysis for 3 of the 4 recipients was consistent with a viral etiology. Neuroimaging and electroencephalogram studies were suggestive of an infectious encephalitis or a toxic encephalopathy. Initial laboratory testing did not demonstrate an infectious etiology. Postmortem histologic analysis, immunohistochemistry, electron microscopy, and direct fluorescence antibody testing revealed rabies virus infection. Serological testing done postmortem confirmed rabies virus infection in the common donor. CONCLUSIONS: These cases demonstrate a risk for transmitting rabies virus infection through solid organ and tissue transplantation, and this diagnosis should be considered in any rapidly progressing neurological disease.

Cadaveric orthotopic auxiliary split liver transplantation and kidney transplantation: an alternative for type 1 primary hyperoxaluria.

Liver transplantation (LTX) corrects the enzymatic defect responsible for type 1 primary hyperoxaluria (PH1). It has been advocated in combination with kidney transplantation (KTX) in patients with renal failure from PH1 because KTX alone can result in early graft loss. A 58-year-old male patient with PH1 on hemodialysis underwent resection of the left lateral segment of the liver followed by orthotopic auxiliary left lateral segment liver transplantation and kidney transplantation from a deceased donor. The serum oxalate dropped from 34.8 micromol/L before transplant to 3.6-8.3 in the first months posttransplant to <1 micromol/L (normal range 0.4-3.0). One year after posttransplant, the patient has an iothalamate glomerular filtration rate of 58 ml/min. Orthotopic auxiliary LTX is an alternative to whole LTX in PH1. By using a split deceased donor liver, it does not deprive the donor pool and protects the recipient from liver failure in case of graft loss.

Transversus abdominis muscle release for repair of complex incisional hernias in kidney transplant recipients.

BACKGROUND: Incisional hernias in kidney transplant recipients (KTRs) can be complex because of adjacent bony structures, proximity of the allograft/transplant ureter, and context of immunosuppression. We hypothesized that our novel posterior component separation with transversus abdominis muscle release (TAR) and retromuscular mesh reinforcement offers a safe and durable repair. METHODS: KTRs with incisional hernias repaired using the aforementioned technique were identified within our prospective database (2007 to 2013) and analyzed. RESULTS: Eleven patients were identified (median age 49 years, body mass index 32). The median hernia size was 30 cm(2) (range 88 to 1,040 cm(2)) and 8 of the 11 patients were recurrent. Intraoperative morbidity consisted of one transplant ureter injury repaired primarily over a stent. Postoperative morbidity consisted of 2 superficial surgical site infections that resolved and 1 readmission for a blood transfusion. There were no instances of mesh infection, explantation, graft loss, or graft dysfunction. With a median follow-up of 12 months (range 3 to 69), 1 (9%) lateral recurrence has been documented. CONCLUSIONS: For complex incisional hernias in KTRs, TAR is associated with low perioperative morbidity and durable repair.

Outcome differences between young children and adolescents undergoing kidney transplantation.

BACKGROUND/PURPOSE: Although graft loss remains the biggest challenge for all pediatric kidney transplant (KT) recipients, unique challenges exist within different age groups. We aim to evaluate the different characteristics and graft survival outcomes of young children and adolescents undergoing KT. METHODS: Children who underwent isolated KT between 2000 and 2013 at our institution were included in this retrospective analysis. Patient characteristics and outcomes were compared using student's t-test, chi-square test, Kaplan-Meier curve and Cox proportional hazards model. RESULTS: Of 73 children who underwent KT, 31 were <12 (young children), and 42 were ≥ 12 years old (adolescents). Overall patient survival was 100%. The younger group had superior 5-year (100% vs. 75.5%) and 10-year (94.4% vs. 43.8%) graft survival (p=0.008). Factors predictive of poor graft survival on multivariate analysis were older age at transplantation (HR 1.2, CI 1-1.4, p=0.047), female gender (HR 9.0, CI 1.9-43, p=0.006), and acute rejection episodes (HR 13, CI 2-90, p=0.008). The most common causes of graft loss were acute and chronic rejection episodes and immunosuppression nonadherence. CONCLUSION: Adolescents undergoing KT have inferior graft survival compared to younger children. In adjusted modeling, children with older age, female gender, and acute rejection episodes have inferior graft survival.

Preoperative and perioperative predictors of the need for renal replacement therapy after orthotopic liver transplantation.

BACKGROUND: Acute renal failure developing after orthotopic liver transplantation (OLTx) requiring renal replacement heralds a poor prognosis. Our center has previously reported a 1-year survival of only 41.8%. We undertook this study to determine whether we could identify preoperative and perioperative factors that would predict which patients are at risk. METHODS: OLTxs performed between January 1, 1996, and December 31, 2001, were included in our retrospective database review. Combined kidney-liver transplants or patients with preoperative renal replacement therapy (RRT) were excluded. A total of 724 OLTxs were studied, which were divided into group I: no RRT, n=637; group II: hemodialysis only post-OLTx, n=17; and group III: continuous RRT post-OLTx, n=70. Univariate and stepwise logistic multivariate analyses were performed. RESULTS: Preoperative serum creatinine greater than 1.9 mg/dL (odds ratio [OR] 3.57), preoperative blood urea nitrogen greater than 27 mg/dL (OR 2.68), intensive care unit stay more than 3 days (OR 10.23), and Model for End-Stage Liver Disease score greater than 21 (OR 2.5) were significant. A clinical prediction model was constructed: probability of requiring dialysis posttransplant=(-2.4586+1.2726 [creatinine >1.9] + 0.9858 [blood urea nitrogen >27] + 0.4574 [Model for End-Stage Liver Disease score >21] + 1.1625 [intensive care unit days >3]). A clinical prediction rule for patients with a score greater than 0.12 was applied to OLTx recipients who underwent transplantation in 2002. A total of 15 of 20 patients who received RRT and 111 of 121 who did not were correctly classified with the model. CONCLUSIONS: This model allowed us to identify patients at high risk for developing the need for RRT postoperatively. Strategies for these patients to prevent or ameliorate acute renal failure and reduce the need for RRT postoperatively are needed.

The changing clinical presentation of recurrent primary biliary cirrhosis after liver transplantation.

BACKGROUND: Recurrent disease after liver transplant is a significant problem. Recurrent primary biliary cirrhosis (RPBC) is a histologic diagnosis. Clinical data is unreliable in predicting or diagnosing recurrence. RPBC appears to have a changing clinical presentation in recent years. MATERIALS AND METHODS: The diagnosis of RPBC after liver transplantation was made histologically. Data were obtained from our prospectively maintained liver-transplant database and evaluated statistically. RESULTS: Between 1985 and 1999, 1,835 liver transplants were performed, 169 for PBC. One hundred fifty-six patients were evaluated (one patient received retransplantation, and 13 were excluded). Seventeen (10.9%) experienced recurrence. Median posttransplantation follow-up time was 72.1 months. Median time to recurrence was 49.6 months. Median follow-up time after recurrence was 11.5 months. Neither acute rejection episodes (P=0.34) nor OKT3 use (P=0.36) before diagnosis of recurrence was significant. The combination of cyclosporine, azathioprine, and prednisolone demonstrated recurrence in 6 of 71 (8.4%). Six of 49 (12.2%) patients treated with cyclosporine with or without mycophenolate mofetil and prednisolone experienced recurrence. Six of 36 (16.7%) patients treated with tacrolimus and prednisolone with or without mycophenolate mofetil experienced recurrence. Patients treated with cyclosporine had numerically fewer recurrences than those treated with tacrolimus (P=0.11). CONCLUSIONS: Patients with RPBC demonstrated prolonged survival. Clinical factors did not aid in predicting RPBC. The clinical course of RPBC appears to be different than in the earlier years of liver transplantation. Immunosuppression may play a role. The use and type of antimetabolite drugs had no affect on recurrence. RPBC demonstrated a different clinical course with tacrolimus treatment (shorter time to recurrence) and increased incidence when compared with cyclosporine treatment. Controlled randomized studies are necessary to determine differences between tacrolimus and cyclosporine treatment, if any.

Fever, infection, and rejection after kidney transplant failure.

BACKGROUND: Patients returning to dialysis therapy after renal transplant failure have high morbidity and retransplant rates. After observing frequent hospitalizations with fever after failure, it was hypothesized that maintaining immunosuppression for the failed allograft increases the risk of infection, while weaning immunosuppression can lead to symptomatic rejection mimicking infection. METHODS: One hundred eighty-six patients with failed kidney transplants were analyzed for rates of hospitalization with fever within 6 months of allograft failure. Patients were stratified by the presence of full immunosuppression versus minimal (low-dose prednisone) or no immunosuppression, before hospital admission. Subsequent rates of documented infection and nephrectomy, as well as patient survival, were ascertained. RESULTS: Hospitalization with fever within 6 months of allograft failure was common, occurring in 44% of patients overall. However, among febrile hospitalized patients who had been weaned off of immunosuppression before admission, only 38% had documented infection. In contrast, 88% of patients maintained on immunosuppression had documented infection (P<0.001). In both groups, dialysis catheter-related infections were the most common infection source. Allograft nephrectomy was performed in 81% of hospitalized patients with no infection, compared to 30% of patients with documented infection (P<0.001). Mortality risk was significantly higher in patients with concurrent pancreas transplants or who were hospitalized with documented infection. CONCLUSIONS: Maintenance immunosuppression after kidney allograft failure was associated with a greater incidence of infection, while weaning of immunosuppression commonly resulted in symptomatic rejection with fever mimicking infection on presentation. Management of the failed allograft should include planning to avoid both infection and sensitizing events.