Pre-transplant predictors of one yr weight gain after kidney transplantation.

Clinically useful predictors of weight gain could be used to reduce the epidemic of post-kidney transplant obesity and resulting co-morbidities. The purpose of this study was to identify predictors of weight gain at 12 months following kidney transplant in a cohort of 96 recipients. Demographic, clinical, and environmental data were obtained at transplant and 12 months. Descriptive, correlational, and Bayesian network analysis were used to identify predictors. For the 52 (55.9%) recipients who gained weight, the average amount gained was 9.18 ± 6.59 kg. From the 15 baseline factors that met inclusion criteria, Bayesian network modeling identified four baseline predictors for weight gain: younger age, higher carbohydrate consumption, higher trunk fat percentage, and higher perception of mental health quality of life. Three are modifiable through either pre- or immediate post-transplant clinical intervention programs.

Blood gene expression profiling in liver transplant recipients with hepatitis C virus and posttransplantation diabetes mellitus.

BACKGROUND: Hepatitis C virus (HCV) is a risk factor for developing posttransplantation diabetes mellitus (PTDM) after liver transplantation; little is known about the biological mechanisms involved with this risk. This study investigated gene expression differences to provide insight into potential mechanisms. PATIENTS AND METHODS: Gene expression profiles of blood samples obtained from 6 HCV+ liver transplant recipients were determined using Affymetrix U133 Plus 2.0 microarrays. Differential gene expression was assessed between HCV+ recipients with PTDM (n = 3) and without PTDM (n = 3) using the GeneSpring 7.3 software package. The Welch t test was used to identify significant differences (P < .05) between groups. Gene expression profiles for 6 HCV- liver transplant recipients (with PTDM = 3, without PTDM = 3) were used as a blind test set to evaluate a subset of genes to predict PTDM. RESULTS: Expression levels of 347 genes were significantly different between recipients with PTDM and those without PTDM. Seventy-four genes were up-regulated and 270 were down-regulated in PTDM. Genes were categorized into functional classes: apoptosis (n = 69 genes); immune function (n = 110); diabetes (n = 17); hepatitis C (n = 12); liver transplant (n = 69). The expression profile of a subset of genes was evaluated for predicting PTDM in 6 HCV- transplant recipients. We accurately predicted the presence or absence of PTDM in 5/6 recipients. CONCLUSIONS: PTDM in HCV+ liver transplant recipients was associated with down-regulated expression of a large number of genes. A subset of these genes was useful to predict PTDM in HCV- recipients. Most genes were associated with apoptosis and immune function. HCV may act as a primer by affecting a group of genes involved in developing diabetes.

Gastroparesis following kidney/pancreas transplant.

This pilot study examined associations among patterns of gastric myoelectrical activity, symptoms of gastroparesis, years of diabetes, months of dialysis, and use of gastrointestinal medications in gastroparetic kidney-pancreas (KP) transplant recipients. Electrogastrography (EGG) and gastric symptom data were obtained from 42 transplant recipients before and after transplant (6, 12, and 24 months). Recipients were 38 +/- 7 yr of age, 88% Whites, and 60% male; 97% had hypertension. All had functioning grafts post-transplant (mean creatinine, 1.59 +/- 0.66 mg/dL, and serum glucose 91.97 +/- 24.92 mg/dL). Sixteen subjects had normal EGG (2.7-3.2 cycles per minute, cpm); two were tachygastric (>3.2 cpm) at all time points; one remained bradygastric (<2.7 cpm) throughout the study period. Following transplant, symptoms lessened and were associated with 6-month normalization of EGG (r = 0.41, p = 0.02). A small change in the percentage of patients with normal EGG was observed from baseline to 24 months (67% vs. 69% respectively); however, there was a shift from bradygastria (29% to 15% respectively) to tachygastria (5% to 15% respectively). Prescribed prokinetic and antisecretory medications use increased over the study period from 13 (31%) subjects at baseline to 32 (86%) at 6 months; 21 (78%) at 12 months; and 12 (92%) at 24 months. Although symptoms diminish following transplant, gastroparesis remains a significant problem for transplant patients. Normalization of EGG and shifts from bradygastria to tachygastria occur post-transplant. Our results suggest that serial EGGs and frequent assessment of symptoms can be used to follow gastroparesis in KP recipients.

Equine vaccine for West Nile virus.

To meet the urgent need of controlling West Nile virus (WNV) infection in the equine population, we have developed a killed WNV vaccine. A dose titration study in horses was first conducted to evaluate serum neutralization antibody responses against WNV in these animals. Horses were vaccinated intramuscularly twice with the test vaccine at low, medium and high dose, three weeks apart. Serum samples were collected periodically and were measured for serum neutralizing antibody using a plaque reduction neutralization test. Significant increases in serum neutralizing antibody were detected in all three dosage groups 14 days post the second vaccination. Twelve months after the second vaccination, horses vaccinated with the medium dose of WNV vaccine and non-vaccinated control horses were experimentally challenged with WNV. Nine out of 11 (81.8%) controls developed viraemia after challenge while only one out of 19 (5.3%) vaccinates had transient viraemia, representing a 94% preventable fraction. In a separate study, the safety of the killed WNV vaccine was demonstrated under field conditions. A total of 648 horses, including 32 pregnant mares, were enrolled in the study. During the two weeks post vaccination period, no local or systemic adverse reactions were observed following 96% of the vaccinations administered while mild, transient injection site reactions were noted in a small number of horses. These results indicate that the killed WNV vaccine developed by Fort Dodge Animal Health is safe and efficacious.

Assessment of the effects of a taped cognitive behavior message on postoperative complications (therapeutic suggestions under anesthesia).

BACKGROUND: The authors studied whether playing a taped cognitive-behavior message during and immediately following bariatric surgery will improve performance of a postoperative regimen designed to enhance recovery. METHODS: The double-blinded placebo-controlled study consisted of 27 morbidly obese bariatric surgical patients randomly assigned to listen to either a blank (Controls) or a positive therapeutic message audiotape (Tape). A Postoperative Regimen Checklist (PRC) quantified different parts of the postoperative recovery regimen. RESULTS: The data showed that patients in the Tape group, compared to the Controls: 1) achieved better scores at most PRC assessment points (p < 0.05), 2) required less encouragement to perform tasks (p < 0.05), and 3) were discharged from the hospital a mean of 1.6 days earlier. CONCLUSIONS: A taped cognitive-behavioral message, played to patients repetitively during and immediately following bariatric surgery, is effective in enhancing postoperative compliance and reducing in-patient length of stay.

A 9-year experience with 126 pancreas transplants with portal enteric drainage.

HYPOTHESIS: A novel technique of pancreas transplantation (PTX) with portal venous delivery of insulin and enteric exocrine drainage (portal enteric) was developed at our center to improve the PTX procedure. DESIGN: Case series. SETTING: Single-center experience at a university hospital. PATIENTS AND INTERVENTION: From October 1990 through December 1999, we performed 126 PTXs with portal enteric drainage, including 90 simultaneous kidney PTXs (SKPT) and 36 solitary PTXs (18 sequential PTXs after kidney transplantation and 18 PTXs alone). MAIN OUTCOME MEASURES: Patient and graft survival rates; medical and surgical morbidity. Three groups, representing 3 eras of immunosuppression, were compared. Thirty patients underwent SKPT with muromonab-CD3 induction and cyclosporine-based therapy in era 1 (October 1990 through June 1995); 42 SKPTs received tacrolimus and mycophenolate mofetil-based immunosuppression without antibody induction in era 2 (July 1995 through May 1998); and 18 SKPTs were performed in era 3 (June 1998 through December 1999) with either basiliximab or daclizumab induction. RESULTS: One-year patient survival rates after SKPT were 77% in era 1, 93% in era 2, and 100% in era 3 (P =.03). The 1-year kidney graft survival rates were 77% in era 1, 93% in era 2, and 94% in era 3 (P =.08). The 1-year pancreas graft survival rates after SKPT were 60% in era 1, 83% in era 2, and 83% in era 3 (P =.06). The incidences of rejection (63% vs. 33% vs. 39%; P<.001) and thrombosis (20% vs. 7% vs. 6%; P<.001) were decreased in eras 2 and 3. CONCLUSION: Simultaneous kidney PTXs with portal enteric drainage can be performed with improved outcomes.

Long-term outcomes in simultaneous kidney-pancreas transplant recipients with portal-enteric versus systemic-bladder drainage.

We retrospectively reviewed long-term outcomes in simultaneous kidney-pancreas transplant (SKPT) recipients with portal-enteric (P-E) versus systemic-bladder (S-B) drainage. Forty-five patients were alive with functioning grafts 1 year after SKPT and were followed up for a minimum of 3 years (mean, 5.9 years), including 26 patients with P-E drainage and 19 patients with S-B drainage. Recipient demographic and transplant characteristics were similar between the two groups. In both groups, hospital admissions decreased significantly with increasing time after SKPT, although significantly fewer readmissions occurred in the first year in the P-E than the S-B group. The most common reason for readmission in both groups was infection, followed by miscellaneous, surgical, and immunologic morbidity. The incidence of readmission for dehydration was significantly less in the P-E group (P < 0.01). Mean systolic and diastolic blood pressures were similar between groups, although the number of antihypertensive medications was significantly less in the S-B group. Although fasting C-peptide levels were significantly greater in the S-B group, the two groups were similar with regard to carbohydrate (fasting serum glucose, hemoglobin A(1c)) and lipid (total cholesterol) metabolism. Renal and pancreas allograft functions were similar between the two groups. At 1 year post-SKPT, stabilization in most diabetic complications was reported. Four quality-of-life surveys that provided 29 scores were completed 6 to 24 months (mean, 18.5 months) after SKPT. Improved quality of life was reported in all but one of the scales, with many dimensions showing significant improvements. At 3 years after SKPT, no activity limitation was reported in 76% of patients with P-E drainage versus 53% with S-B drainage (P = 0.11). Five-year actual patient, kidney, and pancreas graft survival rates after P-E versus S-B drainage are 92% and 84%, 81% and 79%, and 88% and 74%, respectively (P = not significant). SKPT with P-E drainage is a safe and effective method to treat advanced diabetic nephropathy and is associated with decreasing morbidity, improving rehabilitation and quality of life, and stablizing metabolic function over time. The long-term prognosis after the first year is excellent and at least similar to the results achieved with S-B drainage.

Heart rate variability in adolescents and adults with type 1 diabetes.

BACKGROUND: Limited data are available regarding the onset or trajectory of cardiovascular autonomic deterioration in persons with type 1 diabetes. OBJECTIVE: To describe differences in heart rate variability among adolescents with type 1 diabetes, adults with type 1 diabetes who have coexisting renal failure, and adolescent and adult controls. RESEARCH DESIGN AND METHODS: A correlational design was used to compare the status of heart rate variability in adults with type 1 diabetes and renal failure (n = 62); healthy adult controls (n = 67); adolescents with type 1 diabetes (n = 55); and healthy adolescent controls (n = 28). Convenience samples of adult patients with diabetes awaiting kidney or pancreas and kidney transplantation, and adolescents with diabetes were recruited from local university-based clinics. Volunteers served as healthy controls. The short-term R-R variability measures included in this study were changes in heart rate with deep breathing and with the Valsalva maneuver. Twenty-four hour ambulatory heart rate monitoring with power spectral analysis was also obtained to assess longterm R-R variability. RESULTS: Adult patients with type 1 diabetes awaiting transplantation had significantly poorer heart rate variability measures than any of the other three populations studied (p < .0001). Adult control values also were significantly lower than either teenage controls or youths with diabetes (p < .05). Although most long-term R-R variability measures were lower in adolescents with diabetes versus controls, only one measure of parasympathetic modulation (i.e., pNN50) was significantly lower (p = .042). There were significant negative associations between HbA1c and sympathetic modulation (i.e., low hertz) in both the adult group (r= -.406, p = .029) and the adolescent group (r= -.324, p = .025) with diabetes. CONCLUSIONS: Type 1 diabetes is associated with decreased heart rate variability, with the extent of the decrease related to the age of the individual and the severity of the disease.

Lifestyle behaviors affect cardiovascular risk status in men 1 year after kidney transplantation.

Persons with end-stage renal disease have an accelerated risk for cardiovascular (CV) morbidity and mortality. Unfortunately, their accelerated CV risk persists even after kidney transplantation associated with pretransplant and post-transplant vascular disease. number of rejections treated with high-dose steroids, prolonged use of immunosuppressive therapy post-transplant, effects of comorbid chronic conditions and male gender. Unhealthy, modifiable lifestyle practices often augment their CV risk. The purpose of this study was to examine health-related lifestyle behaviors and estimate CV risks of men 1 year following kidney transplantation. Using the Healthier People Network Health Risk Appraisal (HPN-HRA), we examined CV risk characteristics of 34 men (M age=47.3 years) enrolled in an urban, mid-southern transplant center. Participants were assessed via self-administered paper-and-pencil questionnaires and medical record review provided biological data for analyses. HPN-HRA software was used to analyze biological and behavioral characteristics to compute CV risk estimates. Data were analyzed using descriptive, inferential and correlational analyses. The majority of participants reported smoke cessation (n= 19) or never having smoked (n = 8), and consumption of one or less alcoholic drinks per week (n=28). On the other hand, increased risk for heart attack and stroke were associated with advancing age (P<0.0001), white race (P<0.05) and higher systolic blood pressure (P<0.01). While risk for heart attack was associated with current cigarette smoking (P<0.01), risk for stroke was not. Conversely, risk for stroke was associated with higher BMI (P<0.05), risk for heart attack was not. Thus, the study provides evidence that male kidney transplant survivors exhibit a significant number of non-modifiable and modifiable characteristics that contribute to their posttransplant CV risk.

Immunosuppressant side effect profile does not differ between organ transplant types.

Transplantation has enhanced the quality of life of all transplant recipients, but concern remains regarding the side effects of immunosuppressant drugs. In order to respond to these concerns, a survey to ascertain the side effect profile of transplant recipients was undertaken to identify the impact of chronic immunosuppression on quality of life. A nationwide survey of solid organ transplant recipients was carried out using a newly developed immunosuppressant side effect survey. Kidney, kidney-pancreas, liver and heart recipients responded to the survey (n = 505) and reflect the national distribution based on the UNOS data for organ type, recipient race and gender. The survey had four subscales: emotional burden, life/role responsibilities, mobility and GI distress. A fifth subscale included miscellaneous side effects that are more prevalent during the first 2 years post-transplant. Frequency and severity of each side effect were coded on a scale of 0-4 from 'no problem' to 'always' a problem. The entire range of possible scores (0-160) was reported, reflecting adequate variability in the responses. The sample consisted of 51% males, 77% Caucasians, 15% African Americans, with the remaining 8% other races. There were 225 (44.5%) kidney, 147 (29.1%) liver, 101 (20%) heart and 32 (6.4%) pancreas included. Age ranged from 18-71 years with time since transplant 1-21 years. Overall frequency (12.1 +/- 6.08), severity (10.5 +/- 6.96) and weighted scores (25.4 +/- 19.9) were low suggesting that, as a whole, immunosuppressant side effects, while present, were not severe or troublesome for most patients. Side effect profiles appeared similar among organ types. Differences were detected in the GI distress subscale with the heart recipients reporting significantly less GI distress than liver recipients (13.8 vs. 19.2; P<0.05). Side effect impact on mobility tended to increase between time eras; however, no statistical significance was detected. Side effects are a concern among health-care professionals; however, based on the results of this study, immunosuppressant-related side effects are not detrimental to quality of life and show no differences between types of organ transplanted.

Development of a Web site for transplant patient education.

The Internet is a global communication network used by more than 17.6 million adults as a major source of current health information. Both the number of health-related Web sites and the number of Web users are increasing exponentially as well as reports indicating a growth in the number of persons who access the Internet specifically to retrieve information about organ transplantation. However, few are using this medium for posttransplant educational or psychosocial purposes. Armed with this information, as well as a commitment from the transplant team, we chose to develop a Web-based educational program to facilitate posttransplant care for our transplant recipients. The purpose of this article is to describe the planning, development, and implementation of a Web-based education program for transplant recipients.

A center-based approach to a transplant employment program.

The return to work after transplantation has been actively discussed in the transplant community for years. However, despite the desire for transplant practitioners to have recipients return to being healthy, contributing members of society as well as return to work, practitioners often passively support the sick role. We discovered that patients who are returning to work after transplantation may have been out of the work force for several years, and require assistance that we as health care providers were unable or untrained to provide. An employment specialist was added to the transplant staff and became a vital part of our attempts to create a proactive employment atmosphere and enhance our patients' quality of life. Adding an advocate for employment in our center has also facilitated the shift in our thinking and approach to care from the sick role to one of rehabilitation and from reactive to proactive. This change in attitude has assisted in empowering our recipients to feel as if they can truly resume a normal life.

Use of structured self-monitoring in transplant education.

A self-assessment instrument for use at home by transplant recipients was developed to help foster partnership between patients and their healthcare provider. Self-monitoring at home has not replaced the need for close follow-up but does allow patients to provide concrete data to their healthcare provider in order to promote earlier detection of and response to adverse events. Patients are taught the essentials of self-monitoring while they are in the hospital for their transplant. Patients who perform routine self-assessment would be able to detect and provide information about problems early in the course of events. Thus, early intervention could potentially decrease the severity of the problem and prevent repeated hospitalizations. The concern that patients would not be able to perform a reliable self-assessment was unfounded; patients exceeded expectations and embraced the opportunity to communicate physical signs and symptoms effectively.

Posttransplant improvement in heart rate variability correlates with improved quality of life.

A prospective evaluation of 37 kidney and 20 kidney-pancreas transplant recipients was conducted to assess the relationship between pre- to posttransplant changes in heart rate variability (HRV) and quality of life (QoL). Assessments of 24-hour interbeat variability (pNN50 and rMSSD, SDNN, SDANN) and power spectral analysis of total, low (sympathetic), and high (parasympathetic) frequency components of HRV were performed. The Sickness Impact Profile was used to assess three dimensions of QoL (physical, psychosocial, and total functioning) prior to and at 6 months following transplantation. Changes in vagally mediated time domain measures of HRV were related to changes in physical and total functioning. Stronger correlations occurred between biobehavioral measures in kidney-pancreas recipients, with the strongest relationships occurring between changes in HRV frequency domain measures and changes in physical functioning. Findings indicate that changes in HRV and QoL are related, suggesting that interventions that enhance transplant recipients' HRV may also enhance their QoL.

Heart rate variability, mortality, and exercise in patients with end-stage renal disease.

CONTEXT: Cardiac autonomic function has been associated with mortality in patients with end-stage renal disease. It is unknown whether end-stage renal disease patients who have succumbed to sudden cardiac death can be better identified by a newer test of heart rate variability that uses spectral analysis, rather than laboratory evoked measures. OBJECTIVE: This series of studies sought to characterize cardiac autonomic function in patients awaiting kidney transplantation, identify factors associated with heart rate variability, identify tests which distinguish patients at-risk for death, and compare evoked measures with 24-hour heart rate variability measures. PATIENTS: Data were collected on 184 nondiabetics, 60 type 1 diabetics, and 34 type 2 diabetics with end-stage renal disease, all of whom had been referred for kidney transplantation. MAIN OUTCOME MEASURES: The 278 patients and 67 healthy control subjects underwent evoked tests (changes in heart rate with deep breathing and Valsalva maneuver) and 24-hour heart rate variability Holter monitoring (time and frequency domains). Five patients had sudden cardiac deaths during the study. RESULTS: Data showed that end-stage renal disease patients, particularly diabetics, had compromised autonomic function. The standard deviation of all R-to-R intervals for the electrocardiogram recording (< 50 minutes in 60% of the deceased patients), a 24-hour heart rate variability time domain measure, holds the promise of identifying patients at increased risk for death. Exercise was identified as a factor associated with better autonomic function. Examining relationships between 24-hour heart rate variability and characteristics of patients who succumb to death could make quantification of the mortality risk for individual pretransplant end-stage renal disease patients possible, much as it has in other populations. The data from this study may also make it possible to design interventions, such as exercise, aimed at reducing mortality risk.

Choice of surgical technique influences perioperative outcomes in liver transplantation.

OBJECTIVE: To examine how the choice of surgical technique influenced perioperative outcomes in liver transplantation. SUMMARY BACKGROUND DATA: The standard technique of orthotopic liver transplantation with venovenous bypass (VVB) is commonly used to facilitate hemodynamic stability. However, this traditional procedure is associated with unique complications that can be avoided by using the technique of liver resection without caval excision (the piggyback technique). METHODS: A prospective comparison of the two procedures was conducted in 90 patients (34 piggyback and 56 with VVB) during a 2.5-year period. Although both groups had similar donor and recipient demographic characteristics, posttransplant outcomes were significantly better for the patients undergoing the piggyback technique. The effect of surgical technique was examined using a stepwise approach that considered its impact on two levels of perioperative and postoperative events. RESULTS: The analysis of the first level of perioperative events found that the piggyback procedure resulted in a 50% decrease in the duration of the anhepatic phase. The analysis of the second level of perioperative events found a significant relation between the anhepatic phase and the duration of surgery and between the anhepatic phase and the need for blood replacement. The analysis of the first level of postoperative events found that the intensive care unit stay was significantly related to both the duration of surgery and the need for blood replacement. The intensive care unit stay was in turn related to the second level of postoperative events, namely the length of hospital stay. Finally, total charges were directly related to length of hospital stay. The overall 1-year actuarial patient and graft survival rates were 94% in the piggyback and 96% in the VVB groups, respectively. CONCLUSIONS: These data demonstrate that surgical choices in complex procedures such as orthotopic liver transplantation trigger a chain of events that can significantly affect resource utilization. In the current healthcare climate, examination of the sequence of events that follow a specific treatment may provide a more complete framework for choosing between treatment alternatives.

Sustained improvements in cardiac geometry and function following kidney-pancreas transplantation.

Kidney-pancreas (KP) transplantation has been shown to improve left ventricular (LV) geometry and function 6-24 months after the procedure, yet whether these improvements are sustained in long-term survivors has not been demonstrated. This study examined whether early improvements in LV geometry and function were sustained 3-5 years after KP transplantation. Left ventricular function and geometry were prospectively evaluated prior to, and at 1, 2, and 3-5 years posttransplant using two-dimensional, M-mode, echocardiography with Doppler interrogation in the parasternal and apical views. The sample included 21 KP and a comparison group of 12 diabetic kidney-alone (KA) recipients. Long-term (3-5 years) data were obtained for KP recipients only. Although KA recipients had a longer duration of dialysis and worse diastolic function pretransplant, the groups were similar on other baseline measures. KA recipients experienced minimal improvements while KP recipients had significant improvements in cardiac function and geometry, both in terms of mean values and the percentage of KP recipients who experienced normalization posttransplant (p < 0.05). KP recipient improvements were also sustained at 3-5 years posttransplant on three of five measures, with 75% of long-term KP recipients achieving normal LV mass posttransplant compared with 31% pretransplant. Data indicate that significant impairments in cardiac geometry and function occur in diabetic KA and KP recipients. Though both groups experienced early improvements posttransplant, KP recipients achieved more dramatic and clinically significant improvements at 1, 2, and 3-5 years posttransplant. Additional studies are needed to examine the relevance of these findings with regard to the cardiac morbidity and mortality of these patients.