Outpatient Transplant Clinic Research Articles

Sleep disorders, depressive symptoms and health-related quality of life--a cross-sectional comparison between kidney transplant recipients and waitlisted patients on maintenance dialysis

Kidney transplantation is believed to improve health-related quality of life (HRQoL) of patients requiring renal replacement therapy (RRT). Recent studies suggested that the observed difference in HRQoL between kidney transplant recipients (Tx) vs patients treated with dialysis may reflect differences in patient characteristics. We tested if Tx patients have better HRQoL compared to waitlisted (WL) patients treated with dialysis after extensive adjustment for covariables. Eight hundred and eighty-eight prevalent Tx patients followed at a single outpatient transplant clinic and 187 WL patients treated with maintenance dialysis in nine dialysis centres were enrolled in this observational cross-sectional study. Data about socio-demographic and clinical parameters, self-reported depressive symptoms and the most frequent sleep disorders assessed by self-reported questionnaires were collected at enrollment. HRQoL was assessed by the Kidney Disease Quality of Life Questionnaire. Patient characteristics were similar in the Tx vs WL groups: the proportion of males (58 vs 60%), mean ± SD age (49 ± 13 vs 49 ± 12) and proportion of diabetics (17 vs 18%), respectively, were all similar. Tx patients had significantly better HRQoL scores compared to the WL group both in generic (Physical function, General health perceptions, Energy/fatigue, Emotional well-being) and in kidney disease-specific domains (Symptoms/problems, Effect- and Burden of kidney disease and Sleep). In multivariate regression models adjusting for clinical and socio-demographic characteristics, sleep disorders and depressive symptoms, the modality of RRT (WL vs Tx) remained independently associated with three (General health perceptions, Effect- and Burden of kidney disease) out of the eight HRQoL dimensions analysed. Kidney Tx recipients have significantly better HRQoL compared to WL dialysis patients in some, but not all, dimensions of quality of life after accounting for differences in patient characteristics. Utilizing multidimensional disease-specific questionnaires will allow better understanding of treatment, disease and patient-related factors potentially affecting quality of life in patients with chronic medical conditions.

Ocorrência de síndrome hepatopulmonar em pacientes cirróticos candidatos a transplante de fígado

To determine the occurrence of hepatopulmonary syndrome (HPS) in patients with cirrhosis who are candidates for liver transplantation; to compare demographic, clinical, laboratory, and spirometric characteristics, as well as echocardiography results, arterial blood gas analysis, and severity of liver disease between the groups of patients with and without HPS; and to describe the occurrence of HPS in the subgroup of patients with cirrhosis and schistosomiasis mansoni (mixed liver disease). Between January and November of 2007, we evaluated 44 patients under treatment at the Liver Transplant Outpatient Clinic of the Federal University of Pernambuco Hospital das Clínicas, in the city of Recife, Brazil. The diagnostic criteria for HPS were intrapulmonary vascular dilatation, identified by transthoracic echocardiography, and an alveolar-arterial oxygen tension difference >or= 15 mmHg or a PaO2 < 80 mmHg. The mean age of the patients was 52 years, and 31 patients (70%) were male. The most common cause of cirrhosis was alcohol use. Schistosomiasis was present in 28 patients (64%). Of the 44 patients, 20 (45.5%) were diagnosed with HPS. No significant differences were found between those patients and the patients without HPS in terms of any of the characteristics studied. Of the 28 patients with cirrhosis and schistosomiasis, 10 (35.7%) were diagnosed with HPS. In the population studied, HPS was highly prevalent and did not correlate with any of the variables analyzed.

Psychometric re‐evaluation of the immunosuppressant therapy adherence scale among solid‐organ transplant recipients

The objective of this study was to conduct a psychometric re-evaluation of the immunosuppressant therapy adherence scale (ITAS), a self-report measure of immunosuppressant therapy (IST) adherence targeted to solid-organ transplant recipients. Mailed questionnaires were used to collect data from 141 transplant recipients. A factor analysis of the ITAS was conducted. Validity was examined via Pearson's product-moment correlations (r) to theoretically tied measures of social support and resilience. Cronbach's and split-half alpha coefficients determined internal consistency. The response rate was 72.3%. The aggregate mean on ITAS' summed scores was 11.0 (standard deviation = 1.7). The single IST adherence factor had an eigenvalue of 2.92 and accounted for 73% of the scale items' variance. Component loadings for ITAS items were high (> or = 0.80). Zero-order correlations among scale items were moderately strong (> or = 0.57) and significant (P < 0.01). ITAS summed scores were significantly associated with measures of social support and resilience (r > or = 0.20, P < 0.05). Cronbach's alpha was 0.87. The Guttman split-half coefficient was 0.90. This re-evaluation provides needed confirmation that the ITAS is a valid and reliable measure of IST adherence. The ITAS may be useful as an IST adherence measure in the outpatient transplant clinic setting as it is easy to administer, brief and less expensive than many other adherence measures.

Copeptin, a Surrogate Marker of Vasopressin, Is Associated With Accelerated Renal Function Decline in Renal Transplant Recipients

Chronically elevated vasopressin (VP) plasma levels have been shown to induce accelerated renal function decline in rats with chronic renal failure. Whether endogenous VP is a renal risk factor in humans has not been investigated yet. We aimed to investigate whether, in renal transplant recipients, VP concentration is associated with change in renal function during follow-up. In this prospective study, all consecutive patients visiting our kidney transplant outpatient clinic between August 2001 and July 2003 were asked to participate. Serum creatinine was assessed at baseline and at follow-up. Copeptin, the C-terminal portion of the precursor of VP, was determined at baseline (immunoassay). Univariate and multivariate regression analyses were performed to investigate the association between copeptin and renal function decline. Overall, 548 patients were included 6.0 (2.8-11.6) years after transplantation (men 54%, age 52 [43-60] years). Median follow-up was 3.2 (2.7-3.7) years. Median copeptin level was 9.1 (5.0-18.6) pmol/L at baseline. Copeptin was significantly associated with change in estimated Glomerular Filtration Rate (eGFR; MDRD) during follow-up. When our study population was subdivided according to gender-stratified tertiles of increasing copeptin concentration, mean changes in eGFR during follow-up were -0.03, -0.44, and -1.06 mL/min/1.73 m2 per year. In multivariate regression analysis, the association of copeptin at baseline with change in eGFR during follow-up remained significant after adjustment for age, gender, baseline eGFR, and known risk factors for renal function decline. These findings suggest that in renal transplant patients, VP may play a role in renal function decline.

Calcium, phosphate and parathyroid metabolism in kidney transplanted patients

Impaired kidney function is common in kidney-transplanted patients and complications of chronic kidney disease (CKD), such as mineral and bone disorders (MBD) are also prevalent in this population. Similarly to other stages of CKD, increasing evidence supports the association between MBD and cardiovascular risk after kidney transplantation as well. Still, little is known about the prevalence, clinical correlates of MBD and its management in transplanted patients. In this study, we aimed to examine the characteristics of MBD and its associations with clinical parameters in a large prevalent cohort of patients after kidney transplantation. Nine hundred and ninety stable patients followed at a single kidney transplant outpatient clinic were included in the study. Detailed medical history, demographic data and routine laboratory results, including Ca, P and intact PTH were collected. Estimated GFR was calculated using the abbreviated MDRD formula, patients were stratified into three groups based on eGFR. Target levels for Ca, P and iPTH were based on CKD stages according to the NKF-K/DOQI guidelines. Standard statistical procedures, binomial and multinomial regressions were used in the analysis. The mean age was 51 years, 57% were males and 21% were diabetic, with 72 months (median) post-transplantation. Most of the patients were in CKD stage 3. Serum phosphorus showed strong negative correlation with graft function in CKD stages 4-5 (r = -0.633, P < 0.001). Hyperphosphatemia was independently associated with the time spent on dialysis before transplantation, serum iPTH and CKD stages 4-5. iPTH showed negative correlation with eGFR in CKD stages 3-5 (rho = -0.289, P < 0.001) and weak positive correlation with time spent on dialysis prior to transplant (rho = 0.114, P < 0.001). Both hyperparathyroidism (42%) and relative hypoparathyroidism (15%) were frequent. The prescription of P-binders (6%) and vitamin D analogs (33%) was sporadic. Disturbances of bone and mineral metabolism after transplantation are prevalent and are strongly correlated with the kidney function, similarly to non-transplanted CKD patients. MBD in this population is not adequately managed.

Impact of a Pharmacist in the Outpatient Allogeneic Stem Cell Transplant Clinic

Impact of a Pharmacist in the Outpatient Allogeneic Stem Cell Transplant Clinic

Prevalence and correlates of selected alternative and complementary medicine in adult renal transplant patients

The use of complementary and alternative medicine (CAM) has increased considerably in the general population in recent decades. However, the prevalence of CAM use in renal transplant patients has not yet been assessed. To determine the prevalence and correlates of CAM use among renal transplant patients (RTX) who are more than one year post transplant. This secondary data analysis used data from Part 1 of the Supporting Medication Adherence in Renal Transplantation (SMART) study, which tested prevalence, determinants and consequences of non-adherence regarding immunosuppressive medication in kidney transplant (renal TX) patients. The study's convenience sample consisted of 356 patients recruited from two Swiss outpatient transplant clinics during their annual examination visits (mean age: 53+/-13; male: 58%). The use of CAM as well as the specific kind of CAM used was assessed through structured interviews. Assessed CAM use correlates were age, gender, education, depressive symptomatology, comorbidity and smoking status. Relationships between CAM use and candidate correlates were explored using multiple logistic regression. The prevalence of CAM use in this sample of renal TX patients was 11.8%. Most frequently used alternative medicines were Homeopathy (42.9%) and Chinese medicine (23.8%). Two patients used St John's wort. The percentage of patients using Homeopathy (5.1%) and herbal medicine (2%) was similar to that of the general Swiss population (HO: 6.1% & HM: 2.6%). Significant correlates for CAM use were younger age (p=0.017; OR=0.96; 95%CI=0.93-0.99) and female gender (p=0.035; OR=2.13; 95%CI=1.05-4.3). Every eighth renal transplant recipient in this sample used some form of CAM. Of these, some used herbal medicines, of which some are known to interfere with certain immunosuppressive treatment (St John's wort/Chinese medicines). These findings indicate that it is important for health care providers working in renal TX to assess CAM use.

Living Related Kidney Transplantation in Libya: A Single Center Experience

Objective The aim of this study was to establish a successful living related kidney transplantation program in Libya and to bring down health care costs in management of patients with end-stage renal disease. Patients and Methods Since the transplantation program was launched on August 17, 2004, 135 patients have been transplanted up to August 17, 2007. The donors and recipients were screened prior to transplantation. Our immunosuppressive protocol was cyclosporine-based. Both donors and recipients were followed in the transplant outpatient clinic. Results Among 135 accepted pairs, 133 cases (98.5%) were genetically related donors and recipients and 2 cases were emotionally related. Mean donor age was 37 ± 9.5 years (range, 18–56 years). Recipient age was significantly lower, namely, 37 ± 13.6 years (range, 7–67 years). Among the recipients, 95 (70.4%) were males and 40 (29.6%) females, while among the donors, 102 (75.6%) were males and 33 (24.4%) females. The most common donor-recipient relationship was brother-to-brother. There was no early or late surgical mortality among donors. Delayed graft function was observed in 3 patients (2.2%), acute rejection in 6 (4.4%), and posttransplantation infections in 8 (5.9%). Urinary tract infections were diagnosed in 6 patients (4.4%) and pneumonia in 3 (2.2%). Postsurgical complications included ureteric kink in 2 patients (1.5%) and an anastomotic urine leak in 4 (3.0%). At 36 months, graft survival was observed in 130 patients (96.3%) and patient survival in 126 (93.3%). Conclusion The Libyan National Organ Transplant Program has been successful with results comparable to international levels.

Treatment of Anemia in Renal Transplantation: Impact of a Stricter Application of Hemoglobin Targets

Objective The CREATE and CHOIR studies showed a higher risk for cardiovascular events associated with hemoglobin (Hb) values >13 g/dL in patients with stage 3–4 chronic kidney disease. In 2007, a stricter policy on the use of erythropoietin (EPO) was adopted at our center, with an Hb target of 11 to 12 g/dL and withdrawal or reduction of EPO when Hb was >12.5 to 13 g/dL. This study was designed to evaluate this new approach. Materials and Methods The study included patients under follow-up at the transplant outpatient clinic on December 31, 2006 (n = 725), and December 31, 2007 (n = 768). Data were compared between the study populations concerning renal function, Hb, use of EPO, and associated costs. Results No significant differences in creatinine or Hb values were observed between the 2 groups (1.47 ± 0.6 vs 1.42 ± 0.9 mg/dL and 13.7 ± 1.5 vs 13.7 ± 1.6 g/dL, respectively). After implementation of the new protocol, the frequency of severe anemia (Hb <11 g/dL) increased (2% vs 4%; P = .10), the use of EPO decreased (22.1% vs 17.2%; P = .017), and the mean Hb of EPO-treated patients decreased (12.5 ± 1.4 vs 11.9 ± 1.0; P < .001). The Hb target (11–12 g/dL) was met in fewer than one third of patients, with no significant differences between the 2 study times. Conclusions A strict policy on EPO application reduces its use and the rate of patients with “excessive” Hb values (which are associated with increased cardiovascular risks), with an acceptable slight increase in severe anemia cases.

Transitioning health care responsibility from caregivers to patient: A pilot study aiming to facilitate medication adherence during this process

Transition in pediatric transplant recipients consists of both a physical shift in medical care location as well as a transition in health care responsibilities from caregivers to patients. The purpose of the present study was to test the feasibility of a pilot intervention aiming to facilitate the transition in health care responsibilities from caregivers to patients while patients are still receiving pediatric services. Twenty-two patients were enrolled in a two-session educational protocol aiming to facilitate transition of responsibility. Patients were recruited from an outpatient transplant clinic. Ten were referred because of suspected difficulty in transitioning of care, and 12 were consecutively recruited without any specific a priori concerns. Medication adherence, measured through the use of standard deviations of tacrolimus blood levels, and ALT levels were the medical outcome measures. Complete data are available for 20 patients. Mean ALT levels improved after the follow-up period. For referred patients, adherence and ALT levels improved. Standard deviation of tacrolimus decreased from 3.33 to 2.23, t = 2.52, p = 0.04. Mean ALT decreased from 120.33 to 63.99, t = 3.01, p = 0.01. Maximal ALT values decreased overall from 284.10 to 101.20, t = 2.61, p = 0.03. Our findings suggest that targeted education regarding transition in responsibility for adolescents' own health care is feasible in the outpatient environment and may assist families who are facing this potentially challenging process. A randomized, controlled study with a substantial number of enrolled patients is needed to establish the efficacy of this or other approaches.

Anemia Among Long-Term Renal Transplant Recipients

Background The effects of anemia on cardiovascular disease among the end-stage renal disease (ESRD) population suggest that it may be one of the major factors explaining this complication among kidney transplant recipients. Systematic investigation into the prevalence of posttransplantation anemia (PTA) is therefore of critical importance. Materials and Methods This cross-sectional study of data from 650 patients followed at a single outpatient transplant clinic utilized the guidelines of the American Society of Transplantation to define anemia as a hemoglobin (Hb) ≤130 g/L in men or ≤120 g/L in women. Results Among the 39% of patients who were anemic, the prevalence was greater in women than in men. Serum Hb concentrations significantly correlated with the glomerular filtration rate (GFR), serum transferrin, the use of angiotensin converting enzyme inhibitors and mycophenolate mofetil therapy. Upon multivariate analysis, the GFR, serum transferrin, potential nutritional markers, chronic inflammation, and iron deficiency were independently and significantly associated with the presence of anemia. Erythropoietin was administered to 15 (5.7%) anemic patients. Conclusions PTA is a prevalent, undertreated condition. Based on our results, we suggest that protein/energy malnutrition and/or chronic inflammation were independently associated with anemia.

Multi-organ Early Tumor Dissemination After High Urgency Re-transplantation for Hepatocellular Carcinoma in Cirrhosis: Role of Massive Intraoperative Transfusion?

The recurrence rate of hepatocellular carcinoma (HCC) after liver transplantation (LT) ranges between 11 and 18% [1, 2]. Although the role of post-transplant immunosuppression is still unclear [3, 4], most recurrences seem to be related to malignant cells present but not identified at the time of transplantation and/or released during the transplant procedure. Patients whose explanted liver tumors are within currently accepted criteria for transplantation have a low rate of recurrence [5]. While partial tumor necrosis after performance of bridging treatments could result in earlier tumor recurrence post-transplant [6], 100% tumor necrosis is usually associated with very good results [7]. We report on a patient with unexpected multi-organ early tumor dissemination after an initial LT for a complete necrotic HCC in the setting of cirrhosis and a subsequent high urgency re-transplantation for primary non-function. The patient is a 55-year-old man with chronic hepatitis Binduced liver cirrhosis, Child-Turcotte-Pugh class A, and a solitary recurrent HCC meeting the Milan criteria in Segments VI/VIII. The patient had undergone a partial Segment VII resection in December 2003 for a solitary HCC (pT1 G1 V0). Follow-up examinations proved a local recurrence in Segment VI/VIII in January 2005. Further diagnostic workup (abdominal and thoracic computed tomography, bone scintigraphy, positron emission tomography) excluded further tumor manifestations. The patient was evaluated for LT and listed in ‘‘Eurotransplant’’. A computed tomography (CT)-guided radiofrequency ablation was performed for the 4.8 · 3.4 cm HCC in January 2005. Further follow-up studies with CT, magnetic resonance imaging, and positron emissions tomography (PET)-CT showed complete necrosis of the lesion. After a waiting time of 127 days, the patient received a deceased donor full-size liver graft. The last imaging studies were a magnetic resonance imaging and whole-body PET-CT 2 months prior to LT, showing a necrotic area in the ablated liver segment as well as no further malignancy. Intraoperative mismanagement of inferior vena cava and central venous pressure led to excessive bleeding and corresponding transfusion of 46 units of packed red blood cells, plasma, and coagulation factors. Pathological examination of the explanted liver showed 100% necrosis of the HCC lesion as well as no viable tumor in the setting of end-staged liver cirrhosis. The patient experienced primary graft non-function leading to multiorgan failure, and was re-listed as ‘‘high-urgency’’. Three days later he underwent an uneventful re-LT. Neither of the donors had any history or physical evidence of malignancy. After discharge, the patient was followed up at our outpatient liver transplant clinic. The first HCC imaging follow-up at 4 months post-transplant with abdominal and thoracic CT showed no evidence of HCC recurrence. The second HCC follow-up at 8 months post-transplant showed multifocal bilobar intrahepatic HCC recurrence, intraabdominal involved lymph nodes, and multiple bilateral pulmonary and axillary lymph nodes metastases. Percutaneous liver biopsy confirmed the diagnosis of HCC recurrence. Immunosuppression was switched to rapamycin. The patient opted to receive palliative chemotherapy, fully aware of its limited efficacy, and he died 21 months post-transplant. Although the tumor was a well-differentiated HCC without vascular invasion, radiofrequency ablation resulted G. C. Sotiropoulos (&) S. Beckebaum E. P. Molmenti C. G. Klein V. R. Cicinnati C. E. Broelsch M. Malago Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Hufelandstr. 55, 45122 Essen, Germany e-mail: georgios.sotiropoulos@uni-essen.de

49: Metabolic Syndrome in an Outpatient Transplant Clinic Population

49: Metabolic Syndrome in an Outpatient Transplant Clinic Population

Perfil do tratamento da insuficiência cardíaca na era dos betabloqueadores

The inhibition of the rennin-angiotensin-aldosterone system (RAAS) and sympathetic autonomous nervous system has increased the perspective of survival in these patients, as well as allowing the improvement of the quality of life. The aim of this study was to evaluate the reality of the treatment employed and its impact on the disease in patients followed at a specialized heart failure (HF) outpatient clinic. A sample of 96 patients followed at the HF and Transplant Outpatient Clinic of Heart Institute of the University of São Paulo School of Medicine (InCor -HCFMUSP) were evaluated. The data were collected during the ambulatory consultation from the medical files and through physical examination. Patients were randomly selected for the study. Most of the patients were Functional Class II (42.3%) and evolution stage C (94.9%). The medical prescription given to the patients was quite similar to the one recommended by the directives. Approximately 95% of them received RAAS inhibitors (ACE inhibitor--enalapril and captopril--or angiotensin receptor antagonist--losartan), whereas 85% of the patients additionally received beta blockers (carvedilol). The mean dose prescribed was also similar to the one used in large studies and reached more than 60% of the maximum dose for each medication. The hemodynamic data show that patients were stable, despite the intensity of the dysfunction and ventricular remodeling observed in these patients. Patients with HF followed by a specialized medical team receive a medical prescription that is closer to the recommended one. These patients, despite the marked characteristics of disease severity, achieve hemodynamic and clinical stability with an adequate therapeutic optimization.

Prevalence and Impact of Pain on the Quality of Life of Lung Transplant Recipients: A Prospective Observational Study

To study the prevalence and impact of pain on the quality of life (QOL) of lung transplant recipients. Prospective, observational, cross-sectional study. Ninety-six lung transplant recipients (> 3 months after transplantation) completed questionnaires measuring the severity and impact of pain (Brief Pain Inventory), anxiety (State Trait Anxiety Inventory), QOL (Short Form-36 version 2 [SF-36v2]), and depression (Beck Depression Inventory [BDI]). University medical center lung transplant outpatient clinic. The prevalence of pain in lung transplant recipients was 49%. Patients with pain were older, more likely to have undergone unilateral lung transplantation (64% vs 40%, p = 0.03), and were more likely to have lung emphysema (55% vs 38%, p = 0.004). Only a pulmonary diagnosis of lung emphysema remained an independent predictor for postoperative pain in a logistic regression model. Average (+/- SD) score of the BDI was 9.6 +/- 7.8 and 5.8 +/- 5.8 (p = 0.005) for patients with and without pain, respectively. Patients with and without pain did not significantly differ in terms of anxiety. Pain-free patients had a significantly higher physical component score than patients with pain in the SF-36v2 (mean, 48.7 +/- 8.6 vs 38.6 +/- 9.8, p < 0.0001, respectively), while the mental component scores were not statistically different between the two groups. Lung transplant recipients have a high prevalence of pain. Patients with lung emphysema as their preoperative diagnosis are more likely to have pain. The occurrence of pain is associated with a decreased QOL in lung transplant recipients.

Subjective Global Assessment Is a Useful Method to Detect Malnutrition in Renal Transplant Patients

Adequate nutrition is essential for the well-being of renal transplant patients. While body weight gain is a common widely investigated finding, a considerable fraction of patients exhibit poor nutritional status after successful kidney transplantation. In the present study, the prevalence association with nutritional parameters and clinical data of malnutrition among kidney transplant patients were determined based upon a subjective global assessment. This cross-sectional study in the transplant outpatient clinic included 47 patients (10 women, 37 men) of mean age 37.6 ± 10.2 years. The same dietitian performed the assessment on all patients, including anthropometric measurements of body mass index (BMI), mid-arm circumference, and triceps skinfold thickness. The patient data including medications, number of hospitalizations in the preceding year, and presence of chronic allograft failure were collected from medical records. The mean laboratory values during the last 6 months included hemoglobin, creatinine, albumin, phosphorus, C-reactive protein levels, and lipid profile. The patients were classified into 3 groups defined as A (n = 31, 66%), B (n = 11, 23.4%), and C (n = 5, 10.6%), namely, A, no malnutrition versus B/C, moderate or severe malnutrition. Comparison of the 2 groups revealed the serum albumin ( P < .0001), body mass index ( P = .02), and mid-arm circumference ( P = .02) to be higher in group A than groups B/C. Group B/C patients showed higher levels of C-reactive protein ( P < .0001). When compared to the pretransplantation period, the 31 patients in group A included 26 who had increased body mass index after transplantation versus only 3 of 16 patients in groups B/C had ( P < .0001). The hospitalization rates were significantly lower in group A ( P = .02). Additionally, the patients in group A tended to have a lower frequency of chronic allograft rejection when compared to group B/C subjects ( P = .13). In conclusion, assessment of nutritional status of renal transplant patients combined with intervention in the nutritional intake may decrease the morbidity rates in this patient group.

Anemia in kidney transplanted patients

Although a known cardiovascular risk factor, anemia in the renal transplant recipients has only recently been receiving an increasing attention. In a cross-sectional study, data was obtained from 959 patients followed at a single outpatient transplant clinic. Based on the guideline of the American Society of Transplantation, anemia was defined as hemoglobin (Hb) < or =130 g/L in males and < or =120 g/L in females. About one-third (34%) of the patients were anemic. The prevalence of anemia was comparable in males and females. Serum Hb concentration was significantly correlated with the estimated glomerular filtration rate (eGFR) (abbreviated modification of diet in renal disease formula) (r = 0.266, p < 0.001), serum transferrin (r = 0.268, p < 0.001) and serum albumin (r = 0.196, p < 0.001). None of the immunosuppressive medications or the use of angiotensin converting enzyme inhibitors was associated with a higher likelihood of anemia. In multivariate analysis the eGFR, serum albumin and serum transferrin, potential markers of nutritional status and/or chronic inflammation, and also iron deficiency were independently and significantly associated with anemia. Erythropoietin was administered only to 63 (19%) anemic patients. Post-transplant anemia is a prevalent and under-treated condition. Based on our results we suggest that, besides other factors, protein/energy malnutrition and/or chronic inflammation may be independently associated with anemia. Further studies are needed to determine whether the presence of anemia and its treatment will have an impact on long-term outcomes of this population.

Pharmacogenetic association with adverse drug reactions to azathioprine immunosuppressive therapy following liver transplantation

Azathioprine (AZA) is a thiopurine prodrug commonly used in triple-immunosuppressive therapy following liver transplantation. Approximately 1 in 10 patients suffers side effects in response to the drug, the most problematic being bone marrow toxicity. There is evidence that polymorphisms in the genes encoding thiopurine methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPase) predict adverse drug reactions to AZA therapy. Furthermore, common genetic polymorphisms in the gene encoding methylenetetrahydrofolate reductase (MTHFR) may have an indirect impact on thiopurine drug methylation by influencing levels of the methyl donor S-adenosylmethionine (SAM). The aim of this study was to determine whether polymorphisms in these candidate pharmacogenetic loci predict adverse drug reactions to AZA immunosuppressive therapy in liver transplant patients. A series of 65 liver transplant recipients were recruited to the study from the Liver Transplant Out-Patient clinic at The Royal Infirmary of Edinburgh. Clinical response to AZA was retrospectively correlated against TPMT activity, TPMT*2, *3A, and *3A genotypes, inosine triphosphatase (ITPA) 94C>A and IVS2+21A>C genotypes, and MTHFR 677C>T and 1298A>C genotypes. Variant TPMT, ITPA, and MTHFR genotypes were not significantly associated with adverse drug reactions to AZA, including bone marrow suppression. However, the 2 patients who suffered nodular regenerative hyperplasia (NRH) were both heterozygous for the TPMT*3A mutation. In conclusion, our findings suggest that TPMT, ITPA, and MTHFR genotypes do not predict adverse drug reactions, including bone marrow suppression, in liver transplant patients. However, the possible association between NRH and a heterozygous TPMT genotype should be investigated further.

NFLUENCE OF PATIENT AND DONOR MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) 173 G/C, INTRACELLULER ADHESION MOLECULE 1 (ICAM-1) G241R POLYMORPHISM ON LIVER ALLOGRAFT REJECTION: EVIDENCE FROM A SING

Background: Cytokines are key immune mediators and it has been suggested that cytokine gene polymorphisms affecting expression influence rejection or tolerance. Macrophage migration inhibitory factor is a proinflammatory cytokine that plays role in cell mediated immunity and delayed type hypersensitivity. MIF expression is upregulated along with another cytokines such as ICAM-1. The significance of these molecules in the pathogenesis of liver allograft rejection and rejection treatment outcome is not clear. Aim: To determine whether an association exists between gene polymorphisms and liver allograft rejection and rejection therapy outcome. Method: Patients who received a primary liver graft from 2000 onward and were seen at the transplant outpatient clinic since then were included on this study. Frequency data for the polymorphisms in the transplanted group (N = 52) and their matched donors, where available (N = 33), were divided into biopsy proven rejectors (n = 8) and non -rejectors (n = 44). They also compared with a group of healthy controls (n = 140). After informed consent, blood sample was collected and DNA was obtained. Using amplification-refractory mutation system polymerase chain reaction, ICAM-G241R and MIF173G/C gene polymorphisms were performed. Rejection grading was assessed according to Banff criteria. Associations were assessed by using Fisher's exact test. Results: Primary indication for liver transplantation was biliary atresia (n= 12), metabolic liver disease (n = 24), autoimmune hepatitis (n = 6) and the others (n = 10). The median age of patients was 7.7 (ranged; 0.5-16 years). Primary immunosuppression consisted of cyclosporine A in 12 patients and FK-506 in 40 children. Clinically diagnosed rejection was observed in 21 children, 8 of whom were biopsy-proven acute rejection. Median rejection time was 11 days (ranged 6-121). Rejectors most often showed the GG or AG genotype, whereas no rejectors possessed the AA genotype. Univariate analysis showed that polymorphism of ICAM-G241R was significantly related to liver graft rejection. No significant difference was observed in the presence of any genotypes of recipient and donor MIF be tween nonrejectors and rejectors (p = 0.44 and p = 0.27, respectively). When patients were analyzed according to biopsy proven rejectors and non rejectors, we found that polymorphism of recipient and donor ICAM-G241R was significantly correlated to allograft rejection (p = 0.05 and p = 0.05) respectively. The donors whose recipients did not develop rejection had a significant increase of ICAM-G241R GG genotype compared with donors, whose recipients developed rejection episode. On the other hand rejector recipients did not have ICAM-G241R AA genotype compared to nonrejectors. Despite steroid responsive rejectors (n = 13) had more MIF GC genotype than steroid nonresponsive rejectors (n = 8), it did not reach statistically significance (%87.5 vs. %12.5; p = 0.056). Conclusion: There is a relationship between a genetic characteristics and susceptibility to rejection after liver transplantation. According to our preliminary result, recipient ICAM-G241R AA and donor ICAM-G241R GG genotype has preventive role for acute liver allograft rejection. MIF genotype detection may be useful to estimate patients' response to steroid therapy in acute liver allograft rejection.

Relationship Between Immunosuppression and Osteoporosis in an Outpatient Liver Transplant Clinic

Background The aim of this study is to determine the relationship between immunosuppression, disease state, and osteoporosis in an outpatient liver transplant clinic. Methods All liver transplant recipients visiting an outpatient transplant clinic received bone density scanning with a dual-energy X-ray absorptiometry (DEXA) device of the calcaneal bone after completing a questionnaire assessing risk and medications currently being used. Results Of the 137 liver transplant (OLT) recipients completing questionnaires and receiving DEXA screening, patients with low bone density (n = 50) were older (56.6 ± 12.7 years vs 50.2 ± 10.1 years; P = .02) compared with normal density patients (n = 87) and were predominantely female (64.0% vs 35.6%; P = .01). Based on disease state, patients with cholestatic liver failure had lower bone calcaneal area (17.3 ± 1.3 cm 2 vs 18.9 ± 1.57 cm 2; P < .01). Patients taking tacrolimus (n = 112), as compared with cyclosporine (n = 25), had a tendency toward fewer findings of low bone density (37.5% [42 of 112] vs 56.0% [14 of 25]; P = .08) but had more risk factors (3.1 ± 1.2 vs 2.1 ± 0.8; P = .001) and a higher prednisone dose (4.4 ± 5.9 mg/d vs 2.1 ± 3.8 mg/d; P = .026). For patients weaned from prednisone, the tacrolimus patients were less likely to have low bone density (36.2% vs 68.8%; P = .02). Mycophenolate mofetil did not influence bone density or area measured. Conclusions After liver transplantation, patients taking cyclosporine were more likely to have low bone density compared with those taking tacrolimus.