Impact of ureteral stricture and treatment choice on long-term graft survival in kidney transplantation.

We aimed to evaluate the influence of urological complications occurring within the first year after kidney transplantation on long-term patient and graft outcomes, and sought to examine the impact of the management approach of ureteral strictures on long-term graft function. We collected data on urological complications occurring within the first year posttransplant. Graft survivals, patient survival, and rejection rates were compared between recipients with and without urological complications. Male gender of the recipient, delayed graft function, and donor age were found to be significant risk factors for urological complications after kidney transplantation (P < .05). Death censored graft survival analysis showed that only ureteral strictures had a negative impact on long-term graft survival (P = .0009) compared to other complications. Death censored graft survival was significantly shorter in kidney recipients managed initially with minimally invasive approach when compared to the recipients with no stricture (P = .001). However, graft survival was not statistically different in patients managed initially with open surgery (P = .47). Ureteral strictures following kidney transplantation appear to be strongly negatively correlated with long-term graft survival. Our analysis suggests that kidney recipients with ureteral stricture should be managed initially with open surgery, with better long-term graft survival.

Does DCD Donor Time-to-Death Affect Recipient Outcomes? Implications of Time-to-Death at a High-Volume Center in the United States.

For donation after circulatory death (DCD), many centers allow 1 h after treatment withdrawal to donor death for kidneys. Our center has consistently allowed 2 h. We hypothesized that waiting longer would be associated with worse outcome. A single-center, retrospective analysis of DCD kidneys transplanted between 2008 and 2013 as well as a nationwide survey of organ procurement organization DCD practices were conducted. We identified 296 DCD kidneys, of which 247 (83.4%) were transplanted and 49 (16.6%) were discarded. Of the 247 recipients, 225 (group 1; 91.1%) received kidneys with a time to death (TTD) of 0-1 h; 22 (group 2; 8.9%) received grafts with a TTD of 1-2 h. Five-year patient survival was 88.8% for group 1, and 83.9% for group 2 (p = 0.667); Graft survival was also similar, with 5-year survival of 74.1% for group 1, and 83.9% for group 2 (p = 0.507). The delayed graft function rate was the same in both groups (50.2% vs. 50.0%, p = 0.984). TTD was not predictive of graft failure. Nationally, the average maximum wait-time for DCD kidneys was 77.2 min. By waiting 2 h for DCD kidneys, we performed 9.8% more transplants without worse outcomes. Nationally, this practice would allow for hundreds of additional kidney transplants, annually.

Acute cellular and antibody-mediated rejection of the pancreas allograft: incidence, risk factors and outcomes.

Antibody-mediated rejection (AMR) after pancreas transplantation is a recently identified entity. We describe the incidence of, risk factors for, and outcomes after AMR, and the correlation of C4d immunostaining and donor-specific antibody (DSA) in the diagnosis of AMR. We retrospectively analyzed 162 pancreas transplants in 159 patients who underwent 94 pancreas allograft biopsies between 2006 and 2009. Univariate and multivariate analyses were performed to evaluate risk factors for pancreas graft AMR. One-year rejection rates and survival after rejection were calculated by Kaplan-Meier methods. AMR occurred in 10% of patients by 1-year posttransplant. Multivariate risk factors identified for AMR include nonprimary simultaneous pancreas-kidney (SPK) transplant, primary solitary pancreas (PAN) transplant and race mismatch. After pancreas rejection, patient survival was 100% but 20% (8 of 41) of pancreas grafts failed within 1 year. Graft survival after acute cellular rejection (ACR), AMR and mixed rejection was similar. Of biopsies that stained >5% C4d, 80% were associated with increased Class I DSA. In summary, AMR occurs at a measurable rate after pancreas transplantation, and the diagnosis should be actively sought using C4d staining and DSA levels in patients with graft dysfunction, especially after nonprimary SPK and primary PAN transplantation.

The significance of donor-specific HLA antibodies in rejection and ductopenia development in ABO compatible liver transplantation.

The role of humoral alloreactivity in ABO-compatible liver transplantation remains unclear. To understand the significance of donor-specific HLA alloantibodies (DSA) in liver rejection, we applied the currently used strategy for detection of antibody-mediated rejection of other solid allografts. For this purpose we reviewed the data on 43 recipients of ABO identical/compatible donor livers who had indication liver biopsy stained for complement element C4d and contemporaneous circulating DSA determination. Seventeen (40%) patients had significant circulating DSA in association with diffuse portal C4d deposition (DSA+/diffuse C4d+). These DSA+/diffuse C4d+ subjects had higher frequency of acute cellular rejection (ACR) 15/17 versus 13/26 (88% vs. 50%), p = 0.02, and steroid resistant rejection 7/17 versus 5/26 (41% vs. 19%), p = 0.03. Based on detection of the combination DSA+/diffuse C4d+, 53.6% of cases of ACR had evidence of concurrent humoral alloreactivity. Six of the 10 patients with ductopenic rejection had circulating DSA and diffuse portal C4d, three of whom (2 early and 1 late posttransplantation) developed unrelenting cholestasis, necessitating specific antibody-depleting therapy to salvage the allografts. Thus, in ABO-compatible liver transplantation humoral alloreactivity mediated by antibodies against donor HLA molecules appears to be frequently intertwined with cellular mechanisms of rejection, and to play a role in ductopenia development.

A comparison of alemtuzumab with basiliximab induction in simultaneous pancreas-kidney transplantation.

Alemtuzumab is a humanized, rat monoclonal antibody directed against the CD52 antigen. After binding, alemtuzumab causes profound and durable depletion and has been successfully used as immune induction therapy for organ transplantation. This was a single center, retrospective review of patients who underwent simultaneous pancreas-kidney transplantation at the University of Wisconsin using alemtuzumab induction therapy compared with historical controls that received induction with basiliximab. There were no differences in donor or recipient demographics, rates of patient survival, renal or pancreas allograft survival, renal allograft delayed graft function, EBV infection, BKV infection, PTLD or sepsis. There was a statistically significant increase in the incidence of cytomegalovirus (CMV) infection in the alemtuzumab-treated group. Given the significantly higher incidence of CMV infections, we have since altered our induction protocol to consist of a single 30 mg dose of alemtuzumab instead of two doses. The long-term effects of this change remain to be seen. Due to the results seen in this study, the low initial cost of the drug and the absence of any severe, short-term side effects, alemtuzumab has been selected as the induction drug of choice at our center for patients undergoing SPK.

Impact of donor and recipient factors on allograft survival in lung transplantation: A single-center analysis.

BACKGROUND: It remains unclear which donor and recipient factors influence long-term allograft function in lung transplantation (LTx). METHODS: From October 1988 to February 2005, a total of 280 recipients underwent LTx at our center. Donor data and cause of death (CoD) were analyzed. The CoD was categorized according to rate of increase in intracranial pressure at the time of death. Each donor and recipient factor was correlated with long-term graft function. Recipient details, type of transplant, indication for transplant, and time on waiting list were analyzed. Recipients were stratified based on allograft ischemia time (AIT): 0 to 6, 6 to 8, 8 to 10, and >10 hours. RESULTS: Mean donor age was 30.9 years (36.7% male); 49.8% were cytomegalovirus (CMV) positive. Donor CoD was characterized by a slow rise in intracranial pressure (ICP) in 34.4%, rapid ICP in 18.7%, an intermediate ICP in 44.3%, and with no rise in 2.6%. A graft survival benefit was seen with female donors (P = .048); 34.4% of recipients ultimately developed graft failure at long term follow-up. Mean recipient age was 48 years; 63% were male and mean body-mass index (BMI) was 23.6; 60.2% had single lung transplantation, and mean wait list time was 323 days. Mean AIT totaled 421 minutes. Graft survival was longer with AIT of 8 to 10 hours compared to 6 to 8 hours (P = .03). CONCLUSIONS: Donor factor analysis implied only female donor status conferred a long-term graft survival advantage. Intracranial pressure rise differences appear clinically unimportant. Prolonged cold ischemic time (>10 hours) or low recipient BMI did not adversely affect allograft function in our review.

Stable lung allograft outcome correlates with the presence of intragraft donor-derived leukocytes.

BACKGROUND: The role of bone marrow-derived "passenger" leukocytes in the outcome of solid organ transplantation remains controversial. This study tested the relationship between high levels of donor-derived leukocytes within the transplanted organ and clinical outcome after lung transplantation. METHODS: Sequential bronchoalveolar lavage samples were obtained from human lung allograft recipients. Leukocytes of donor origin in the bronchoalveolar lavage fluid were detected using two-color immunofluorescence, and the results were correlated with multiple clinical parameters. RESULTS: Mean donor leukocyte levels for the first 200 days after transplantation were higher in patients with a good transplantation outcome compared with those patients who lost their grafts due to acute rejection (AR) or developed bronchiolitis obliterans syndrome. The presence of low numbers of donor-derived leukocytes for the first 200 days after transplantation was found to be a significant risk factor for graft loss due to either acute or chronic rejection (P=0.032). Nearly all patients (85%) experienced AR episodes. However, the time to onset of severe AR episodes was significantly longer (P=0.049), and the incidence of these episodes reduced, in patients who maintained high numbers of donor-derived leukocytes for the first 200 days after transplantation. CONCLUSIONS: The presence of high numbers of donor-derived leukocytes, particularly macrophages, in the transplanted lung in the first 200 days after transplantation was associated with stable graft function. Donor-derived leukocytes were reduced or absent in patients with a poor transplantation outcome. These findings rule out a negative influence of persisting donor leukocytes and are consistent with the emerging two-way models of transplant tolerance.

The impact of hypoalbuminemia in kidney-pancreas transplant recipients.

BACKGROUND: Hypoalbuminemia is associated with poorer outcomes in renal transplantation. Diabetes can compound hypoalbuminemia's detrimental effects. Kidney-pancreas transplantation alters the diabetic milieu; yet, some patients continue to be hypoalbuminemic. METHODS: We retrospectively analyzed 232 patients who underwent simultaneous kidney-pancreas transplantation (SPK) between 1993 and 1997 to determine the incidence and clinical correlates of hypoalbuminemia in SPK recipients. Post-SPK hypoalbuminemia was defined as a serum albumin level < or =3.5 g/dl. Univariate analyses were performed to determine whether post-SPK hypoalbuminemia was associated with pre-SPK variables. The effect of albumin level and hypoalbuminemia on the risk of post-SPK events (cardiac events, cytomegalovirus [CMV] infection, rejection, readmission, kidney and pancreas graft failure, and death) was examined with a Cox proportional hazards model. RESULTS: The study population consisted of 149 men and 83 women. Average follow-up was 2.0+/-1.3 years. Hypoalbuminemia (serum albumin level < or =3.5 g/dL) was most common early after SPK (3 months: 44% of evaluable patients were hypoalbuminemic; 12 months: 15.3%; 36 months: 8.3%). Acute rejection episodes and readmission were the most common adverse events after SPK transplantation. There were 24 episodes of renal allograft loss and only 5 cardiac events. Ten SPK recipients died during the study time period. SPK-related hypoalbuminemia was associated with an increased risk for CMV infection (risk ratio [RR] 2.5; P<0.02), renal graft failure (RR 2.41; P=0.05), pancreas graft failure (RR 3.66; P=0.01), and a trend toward an increased risk for death (RR 2.8; P=0.19). CONCLUSIONS: Post-SPK hypoalbuminemia resolves over time in many patients. Persistent post-SPK hypoalbuminemia is associated with an increased risk for CMV infection, graft loss, and a trend toward decreased survival. Efforts to improve nutrition, as it may affect hypoalbuminemia in SPK recipients, may be one strategy for improving SPK outcomes.

Nasal irrigation for the alleviation of sinonasal symptoms.

OBJECTIVE: To determine the effect of nasal irrigation on sinonasal symptoms. STUDY DESIGN AND SETTING: A total of 150 adult subjects with chronic sinusitis symptoms were recruited from the community and assigned to 1 of 3 treatment groups: nasal irrigation with bulb syringe, nasal irrigation with nasal irrigation pot, or control treatment with reflexology massage. Groups 1 and 2 performed daily hypertonic saline irrigation with 1 device for 2 weeks and then with the other device for 2 weeks. Group 3 performed reflexology massage daily for 2 weeks. Prospective data collected included pretreatment Medical Outcomes Study Short Form, pretreatment and posttreatment Rhinosinusitis Outcomes Measure, daily medication use, subjective treatment efficacy, and preference of irrigation method. RESULTS: There was a significant and equivalent improvement in Rhinosinusitis Outcomes Measure 31 score after 2 weeks of intervention in each treatment group; 35% of subjects reported decreased use of sinus medication. CONCLUSION: Daily nasal irrigation using either a bulb syringe, nasal irrigation pot, and daily reflexology massage were equally efficacious and resulted in improvement in the symptoms of chronic sinusitis in over 70% of subjects. Medication usage was decreased in approximately one third of participants regardless of intervention.

Obstructive sleep apnea in children with achondroplasia: surgical and anesthetic considerations.

OBJECTIVE: To evaluate the prevalence of obstructive sleep apnea in a large population of children with achondroplasia and to evaluate the effectiveness of adenoidectomy and/or tonsillectomy as treatment. METHODS: Retrospective review of 95 children with achondroplasia. RESULTS: Thirty-six patients (38%) had clinical evidence of obstructive sleep apnea. Thirty-four patients underwent surgery, with more than 1 procedure required in 10 children (29%). Adenotonsillectomy was the initial procedure for 22 of 34 patients, and further therapy was required in only 18% of this group. Adenoidectomy was the initial procedure for 10 of 34, with 90% requiring further surgery for recurrent obstructive sleep apnea. Tonsillectomy alone was performed in 2 patients: 1 was effectively treated and 1 later required adenoidectomy. Endotracheal intubation was accomplished in all patients without complication; 53% required a smaller endotracheal tube than would be predicted by their age. Eight postoperative complications were recorded. CONCLUSIONS: Obstructive sleep apnea is very common in children with achondroplasia. Surgery is effective, but recurrent symptoms are common, particularly when the initial procedure is adenoidectomy. The complication rate is higher than that observed in a general pediatric population but is readily managed with standard therapy. Anesthesia can be given safely to these patients with special consideration for limited neck extension and appropriate endotracheal tube size.

Combined hepatocyte-selective and blood-pool contrast agents for the CT detection of experimental liver tumors in rabbits.

PURPOSE: To determine the imaging characteristics of a new computed tomographic (CT) contrast material with both hepatocyte-selective and blood-pool components (iodinated triglyceride (ITG)-dual) versus standard iohexol. MATERIALS AND METHODS: VX2 carcinoma was inoculated in seven rabbits. Animals underwent nonenhanced, iohexol-enhanced (600 mg of iodine per kilogram of body weight), and ITG-dual-enhanced (blood-pool moiety, 100 mg of iodine per kilogram; hepatocyte-selective moiety, 100 or 200 mg of iodine per kilogram, injected 90 minutes apart) helical CT. Livers were removed, preserved in formalin, suspended in agar, and sectioned transversely at 3-mm intervals. Attenuation values for normal liver and tumors were obtained, and blinded readers evaluated images for lesions by using a modified free-response receiver operating characteristic (ROC) method. RESULTS: A total of 47 separate tumor sites were detected at pathologic examination. ITG-dual-enhanced scans obtained with 300 mg of iodine per kilogram demonstrated similar liver opacification to iohexol-enhanced scans obtained with 600 mg of iodine per kilogram, but with less lesion enhancement, which resulted in better liver-to-lesion contrast. Blinded readers had a higher sensitivity, accuracy, and area under the ROC curve for ITG-dual-enhanced scans as compared with iohexol-enhanced scans (P: <.01). CONCLUSION: ITG-dual-enhanced CT quantitatively and qualitatively improved liver lesion detection versus iohexol-enhanced CT. Future clinical trials with various human tumor types after potential approval for human use are needed to determine the ultimate role of this or other dual-mechanism contrast materials.

Pancreas transplantation at the University of Wisconsin.

Based on the University of Wisconsin experience with 653 cadaver pancreas transplant performed since 1985, we noted that: 1. The overall 5- and 10-year patient survival rates were 87% and 80%, respectively. The 5- and 10-year pancreas graft survival rates were 70% and 60%, respectively, and the 5- and 10-year kidney graft survival rates were 80% and 60%, respectively. 2. An immunosuppressive regimen including TAC and MMF in both solitary pancreas and SPK transplants was very effective in reducing the rate of acute rejection and improving graft survival. 3. Pancreas graft survival in recipients of solitary pancreas transplants was equivalent to that in SPK recipients in the TAC-MMF era. 4. Anti-IL2 receptor monoclonal antibodies were safe and effective in solitary pancreas and SPK transplants. 5. Excellent short-term graft survival can be achieved in solitary pancreas transplants using enteric drainage.

Simultaneous pancreas-kidney transplantation reduces excess mortality in type 1 diabetic patients with end-stage renal disease.

BACKGROUND: Diabetic renal disease continues to be the most significant cause of end-stage renal disease (ESRD) in the United States. Renal transplantation improves diabetic ESRD patient survival; however, the diabetic state remains associated with poor patient survival. Simultaneous pancreas-kidney (SPK) transplantation can restore normoglycemia and thus may improve outcomes. METHODS: We assessed the impact of SPK on age-range-matched type 1 diabetic patients who underwent renal transplantation at a single center. The observed/expected life span and annual mortality rates (AMRs) were used as measures of survival. A Cox proportional hazards analysis was used to analyze the impact of potential variables on mortality in SPK recipients. RESULTS: SPK transplantation (N = 335) increased the observed/expected life span compared with diabetic cadaveric (DM-Cad, N = 147) and live-donor (DM-Live, N = 160) transplant recipients (P = 0.004) and significantly reduced the AMRs (SPK, 1. 5%; DM-Cad, 6.27%; DM-Live, 3.65%, P = 0.008, SPK vs. other DM). Moreover, the SPK observed/expected life span and AMR were not significantly different from that of age-range-matched nondiabetic transplant recipients (N = 492). The only variable that was significantly associated with patient survival was discharge serum creatinine (relative risk 1.16, P < or = 0.0154). CONCLUSION: These data demonstrate that SPK improves the ability for type 1 diabetic patients to live more of their expected life span. This suggests that glycemic control, even as a late intervention in a diabetic patient's lifetime, may beneficially affect survival.