Is surviving enough? Coping and impact on activities of daily living among melanoma patients with lymphoedema.

We assessed the impact of lymphoedema (defined as ≥ 10% limb volume change) on quality of life (QOL), ability to perform activities of daily living (ADLs) and coping in 277 melanoma patients. Limb volume was measured prospectively, pre-operatively and every 3-6 months for 18 months post-operatively using a perometer. Three questionnaires were administered to measure QOL, coping and impact on ADLs. Statistical analyses were conducted using longitudinal logistic regression models. At 18 months, the cumulative incidence of lymphoedema was 31% in patients with upper extremity nodal basin treatment and 40% in lower extremity nodal basin treatment patients. Patients with lower extremity lymphoedema reported lower QOL scores than those with upper extremity lymphoedema. Over 18 months, both groups with mild and moderate lymphoedema showed improvement in coping [odds ratio (OR): 6.67, 95% confidence interval (CI): 3.30-13.47] and performance of ADLs (OR: 7.46, CI: 3.38-16.47). Over the course of 18 months, men were found to have poorer coping scores than women (OR: 2.91, CI: 1.35-6.27). Lymphoedema was associated with improvement in coping over time (P = 0.08) and a higher reported interference with ADLs (OR: 2.53, CI: 1.29-4.97). Patient education about lymphoedema at the time of surgical consent may improve self-efficacy and coping ability. Effective management of lymphoedema may improve patient QOL and reduce interference with ADLs.

BK virus infection in association with posttransplant urothelial carcinoma.

OBJECTIVE: BK virus infection after transplantation is known to cause graft failure but the association with malignancies is controversial. METHODS: BK virus workup was performed for kidney recipients in our center under conditions of hematuria or acute deterioration of graft function. We reviewed the history and reported our treatment and the disease course of three patients with BK virus later diagnosed with urothelial carcinoma. RESULTS: All three patients received kidneys from China with immunosuppression using a calcineurin inhibitor and monoclonal antibodies. Synchronous bladder and upper-tract tumors were treated with surgery followed by intravesical chemotherapies. We tapered the immunosuppressants and changed to a sirolimus-based regimen. Intravesical chemotherapy and concurrent chemoradiotherapy were performed to prevent recurrence. All three patients now have functional grafts. CONCLUSION: BK virus infection may lead to tumorigenesis. Besides decreasing immunosuppressants, we should be more alert to the detection of malignancies in BK virus-reactivated recipients. Early aggressive treatment may be curative, preserving functional grafts.

Techniques of vascular control in laparoscopic donor nephrectomy.

OBJECTIVES: Laparoscopic donor nephrectomy has become the method of choice for removal of living donor kidneys. The ENDO GIA stapler is commonly used for division of the renal vessels, but it can lead to some loss of graft vascular length. Besides, stapler malfunction can occur. In this study, we report our experience using polymer locking clips for vascular control, compared with previous experience using the ENDO GIA stapler. MATERIALS AND METHODS: Eleven donors underwent laparoscopic donor nephrectomy from November 2005 to September 2007. Both renal artery and vein were divided after 2 or more polymer locking clips had been applied on the donor side. The operative times, warm ischemia times, graft function, and vascular complications were compared with the previous 33 donors using the ENDO GIA stapler for renal vein control. RESULTS: The operative and warm ischemia times were similar. With the polymer locking clip technique, we harvested nearly the entire renal vein length. There were no vascular complications or graft loss with the use of polymer locking clips. In our series, malfunction of the ENDO GIA stapler device occurred in 1 patient requiring the surgery to be converted to an open procedure. Both donor and recipient outcomes were similar no matter whether polymer locking clips or the ENDO GIA stapler was used for vascular control during the laparoscopic donor nephrectomy. CONCLUSION: In our series, there were no vascular complications and no device failure during vascular control using polymer locking clips. We believe that polymer locking clips are safe, yielding greater vessel length during laparoscopic donor nephrectomy.

HLA class I antibodies in patients awaiting kidney transplantation and the association with renal graft survival.

The presence of alloantibodies against human leukocyte antigens (HLA) in the circulation of a transplant recipient shows a significant negative impact on the outcome of solid-organ transplantations. The aim of this study was to examine the impact on renal graft survival of various patterns of alloantibodies detected among patients awaiting kidney transplantation. Among more than 2000 patients awaiting kidney transplantations between July 1992 and March 2006, were 683 patients who displayed anti-HLA alloantibodies, 318 of whom were enrolled in this study. Each patient was followed for at least 9 months; the presence of HLA alloantibodies was checked every 3 months by an enzyme-linked immunosorbent assay. Among these 318 patients, 55 patients underwent kidney transplantations. Their median follow-up time was 69 (range, 9-129) months, including 267 (84%) who displayed persistent class I HLA alloantibodies. The intermittent presence of class I HLA alloantibodies was seen in 20 (6.3%) patients. Serum class I HLA antibodies which was positive at first then became undetectable in 4 (1.3%) patients. Three (0.9%) patients were unsensitized at first and then developed class I HLA alloantibodies later; & 24 (7.5%) patients had class I HLA alloantibodies only once during the follow-up period. Among these patients, 55 patients received renal transplantations. The median survival time was shortest in the patients with persistent class I HLA alloantibodies (59.9 months) and longest among patients who were positive at first and then became negative thereafter or in whom class I HLA alloantibodies was detected only once (132 months). There was a significant difference in graft survival times between patients who had persistent HLA alloantibodies and those in whom to have class I HLA alloantibodies were detected only once (P < .05). In this study, the persistent presence of class I HLA alloantibodies among pretransplantation patients was associated with poorer renal graft outcomes. Surveys of various patterns of sensitization to class I HLA antigen may help us to perform risk stratification. High-risk patients may need more aggressive approaches to deplete antibody or complement levels.

Sirolimus conversion experience in a single center.

OBJECTIVE: One major cause of graft loss is chronic allograft nephropathy (CAN), which may relate to calcineurin inhibitors (CNIs). We converted CAN cases from CNIs to sirolimus and observed the outcomes. METHOD: From January 2004 to August 2007, there were 28 kidney recipients in our center with creeping creatinine levels compatible with CAN. We started sirolimus at 2 mg/d and reduced the CNIs gradually. Sirolimus trough levels were kept between 5 and 8 ng/mL. Mycophenolic acid was cut in half; there was no adjustment on prednisolone dose. RESULTS: The mean switch time was 47.3 months after transplantation. One case discontinued sirolimus due to severe drug-induced pneumonitis. Twelve of the 27 (45%) patients showed improvements in graft function. The most frequent complications were anemia (13/28), hyperlipidemia (13/28), and pneumonitis (4/28). A baseline serum creatinine level less than 2.2 mg/dL seemed to forecast a response to sirolimus conversion. Most of the graft functional improvement occurred within 6 months after the switch. No graft or patient loss was encountered. CONCLUSION: Our experience suggested that 45% of patients with sirolimus conversion showed improved graft function. Among patients within 1 year after transplantation, those with a creatinine level less than 2.2 mg/dL, no proteinuria, and no hyperlipidemia seemed to be better candidates for Sirolimus conversion.

Hepatocellular carcinoma following renal transplantation: experience in northern Taiwan.

BACKGROUND: Transitional cell carcinomas (TCC) have been reported to be the most common post-renal transplantation malignancy in Taiwan; they are considered to be related to the use of herbal drugs. However, in 2004, hepatocellular carcinoma (HCC) was the most prevalent malignancy at our institute. We therefore extended our observations through 2006 to include a larger renal transplant cohort. MATERIALS AND METHODS: Patients were given an immunosuppressive regimen consisting of either cyclosporine or FK 506, mycophenolate mofetil, and copticosteroid. Critical diagnostic follow-up procedures were performed trimonthly. Aggressive surgical procedures were performed when operable cancers were found. Immunosuppressants were reduced thereafter to prevent recurrence. RESULTS: Among 663 patients, 55 developed 58 malignancies which were diagnosed after a mean of 70 months posttransplantation. Among these 55 patients, 25 died. HCC accounted for 22 malignancies, followed by 15 cases of TCC, and 8 cases of posttransplantation lymphoproliferative disorder (PTLD). Fifteen known hepatitis B carriers received lamivudine therapy; none had recurrences and only 2 acquired HCC. These 2 patients are still living, whereas the remaining 20 subjects with HCC are deceased. Of the 37 patients who received anti-CD25 induction therapy, none displayed PTLD. CONCLUSIONS: HCC remains the most common post-renal transplantation malignancy in northern Taiwan. The high rates of hepatitis B and C endemic to Taiwan and the prevalence of hepatitis C virus (HCV) genotype 1b infections in northern Taiwan may explain this finding. Frequent alpha-fetoprotein measurements and liver ultrasonograms are recommended for early detection of HCC among Taiwanese renal transplant recipients. Anti-CD25 induction therapy appears to be helpful to prevent the development of PTLD among Taiwanese renal transplant recipients.

Sirolimus used during pregnancy in a living related renal transplant recipient: a case report.

OBJECTIVES: The majority of pregnancies after transplantation reported in the literature occurred in patients treated with a combination of calcineurin inhibitors, prednisolone, and azathioprine. There is little experience with newer drugs. We report a successful pregnancy in a kidney recipient with exposure to sirolimus-based immunosuppression. METHODS: We describe a case of successful delivery in a 30-year-old woman who became pregnant 1 year and 8 months after a living related renal transplantation. She received sirolimus, cyclosporine, and prednisolone before conception and during the first and second trimesters of gestation. RESULTS: The female recipient received sirolimus in combination with cyclosporine and prednisolone. During follow-up, her serum creatinine values were stable with pregnancy occurring at 1 year and 8 months after transplantation. At 27 gestational weeks, sirolimus was discontinued and she was maintained on cyclosporine and prednisolone. There were no signs or symptoms of graft rejection. A Cesarean section was performed at 39 weeks of gestation to deliver a healthy, 2994-g, Apgar 10, male infant. The renal function of the female recipient continued to be stable after delivery. CONCLUSION: To date, pregnancies in renal transplant recipients are still considered high risk. The U.S. National Transplantation Pregnancy Registry (NTPR) has reported increased rates of maternal and fetal complications. There have been no live births reported to the NTPR about female recipients exposed to sirolimus throughout gestation. We report a live birth without a structural defects with successful delivery after sirolimus use during the first and second trimesters of gestation.

Osteoporosis after kidney transplantation: preliminary report from a single center.

OBJECTIVE: One of the major adverse effects of kidney transplantation is osteoporosis, which is mainly related to steroid use. Only limited data are available on calcitonin therapy for posttransplantation osteoporosis. METHOD: From March 2007 to August 2007, 67 kidney recipients agreed to enter this study. Dual energy X-ray absorptiometry (DEXA) was performed to evaluate bone mineral density (BMD) in the lumbar (L) spine and left femoral neck. We prescribed calcitonin nasal spray to osteoporosis patients (DEXA T < -2.5 SD) who agreed with the treatment. A second and a third DEXA were performed at 3-month subsequent intervals later to evaluate the therapeutic effects. RESULTS: The incidence of osteoporosis in our kidney recipients was 46.26% (31/67 patients). Osteopenia accounted for 38.81% (26/67 patients) and only 14.93% (10/67 patients) were normal. Calcitonin inhalation seemed to improve the BMD with 61% showing improvement on the second DEXA study in our preliminary data. CONCLUSION: Our preliminary data suggested that calcitonin may help to restore bone mass in kidney recipients with osteoporosis. Steroid elimination may prevent the onset of osteoporosis and might even enhance calcitonin efficacy. In the future we need a longer study period to confirm the results and compare it with the outcomes of bisphosphonates therapy.

Geriatric Nutritional Risk Index, a Simplified Nutritional Screening Index, Is a Strong Predictor of Handgrip Strength in Renal Transplant Recipients.

BACKGROUND: The Geriatric Nutritional Risk Index (GNRI) is a useful predictor of prognosis in older patients and those receiving hemodialysis. However, the predictive value of the GNRI in renal transplant recipients (RTRs) is unclear. In this study we investigated the correlation between the GNRI and muscle function, as indicated by handgrip strength (HGS). METHODS: A cross-sectional study was performed on 42 RTRs (50% women), with a mean age of 49.0 ± 10.8 years. The GNRI was derived from patients' body weight and serum albumin level by using the following equation: GNRI = [14.89 × albumin (g/dL)] + [41.7 × (body weight/ideal body weight)]. HGS was evaluated in dominant arms; HGS measurement was repeated 3 times, and the highest value was used. Multivariable stepwise regression analyses were performed to obtain adjusted correlates, and the significance levels for entry and remaining were set at 0.1. RESULTS: The mean values of the GNRI and HGS were 105.0 ± 5.4 and 29.0 ± 9.4, respectively. The GNRI was positively correlated with HGS (r = 0.36, P = .02). Linear and stepwise multivariable adjustment analyses revealed that the homeostatic model assessment of insulin resistance (HOMA-IR) and GNRI were independent determinants of HGS (ßHOMA-IR = 0.53 and ßGNRI = 0.43, adjusted R2 = 0.45) after adjustment for age, sex, total muscle mass, and C-reactive protein level as covariates. CONCLUSION: This study has shown that the GNRI is a favorable predictor of muscle function in RTRs.

Effective Decision-Making and Decisional Regret in Living Kidney Donors of Taiwan.

BACKGROUND: While most living kidney donors are satisfied with their decision and do not regret donating, few studies have been conducted on the determinants related to the effectiveness and regret of the decision. This study aims to explore the relationship between basic attributes, quality of life, positive affect, negative affect, effectiveness of decision-making, and regret in living kidney donors. METHODS: In this cross-sectional study, living kidney donors were recruited from urology and kidney transplant outpatient services. The structured questionnaire used to collect the data included the Positive and Negative Affect Schedule, Medical Outcomes Study 12-Item Short-Form Health Survey, Decision Conflict Scale, and Decision Regret Scale. RESULTS: The findings indicate that living donors with better health status, 24-hour creatinine clearance, physical health-related quality of life (HRQOL), and positive affect experienced greater feelings of effective decision-making. Moreover, women and donors with better physical HRQOL, positive affect, and decision effectiveness were less regretful about the decision of kidney donation. CONCLUSION: Health status, physical HRQOL, and positive affect are related to decision validity and regret of living donors. Therefore, clinical care providers should regularly assess the mood and health of living kidney donors. Furthermore, activities promoting their health should be encouraged, especially for men.

CREB is one component of the binding complex of the Ces-2/E2A-HLF binding element and is an integral part of the interleukin-3 survival signal.

The Ces-2/E2A-HLF binding element (CBE) is recognized by Caenorhabditis elegans death specification gene product Ces-2 and human acute lymphocytic leukemia oncoprotein E2A-HLF. In an attempt to identify a cellular CBE-binding protein(s) that may be involved in apoptosis regulation in mammals, multiple nuclear binding complexes of CBE were identified in various mammalian cell lines and tissues by electrophoretic mobility shift assay. Cyclic AMP (cAMP)-responsive element (CRE)-binding protein (CREB) was present in one major CBE complex of Ba/F3 and TF-1 cells, and both in vitro-translated and Escherichia coli-synthesized CREB bound to CBE. Activation of CREB by cAMP-elevating chemicals or the catalytic subunit of protein kinase A (PKAc) resulted in induction of the CBE-driven reporter gene. Stimulation of Ba/F3 cells with interleukin-3 (IL-3) promptly induced phosphorylation of CREB at serine(133) partially via a PKA-dependent pathway. Consistently, Ba/F3 cell survival in the absence of IL-3 was prolonged by activation of PKA. Conversely, treatment of cells with a PKA inhibitor or expression of the dominant negative forms of the regulatory subunit type I of PKA and CREB overrode the survival activity of IL-3. Last, the bcl-2 gene was demonstrated to be one candidate cellular target of the CREB-containing CBE complex, as mutations in the CRE and CBE sites significantly reduced the IL-3 inducibility of the bcl-2 promoter. Together, our results suggest that CREB is one cellular counterpart of Ces-2/E2A-HLF and is part of IL-3 dependent apoptosis regulation in hematopoietic cells.

Positive and Negative Affects in Living Kidney Donors.

OBJECTIVE: This study aimed to identify the factors influencing the positive and negative affects and the health-related quality of life (HRQOL) of living kidney donors. METHODS: With the use of a cross-sectional study design and a structured questionnaire, information on the basic characteristics, positive affect, negative affect, and HRQOL of 41 living kidney donors were compared. RESULTS: The negative affect in living kidney donors was similar to that of the general population, but the positive affect was slightly lower. The physical HRQOL of living kidney donors was slightly higher than that of the general population, and the mental HRQOL was similar. Female donors showed a greater positive affect than male donors. The donors who were siblings of the recipients showed a more negative affect. Donors without chronic disease and with good perceived physical health showed improved positive affect, negative affect, and mental HRQOL. Furthermore, living kidney donors with better positive and negative affects showed improved physical and mental HRQOLs. CONCLUSIONS: Clinical health providers should evaluate and determine the positive affect, negative affect, and quality of life of living kidney donors, especially in men, siblings of the recipients, those with chronic disease, and those with poorer perceived physical health. Moreover, psychosocial interventions should be provided to improve these factors.

Preoperative evaluation of living related kidney donor: which kidney to donate?

OBJECTIVES: As the number of cadaveric donor is far beyond the demand of the waiting list, living related kidney transplantation is important for the worldwide organ shortage. Besides, living related transplantation has advantages compared with cadaveric transplantation in terms of graft function and survival. However, the remaining kidney function of the living donor needs to be evaluated. METHODS: We collected 28 paired living kidney donations from March 2003 to March 2005. All patients underwent laparoscopic donor nephrectomy. The preoperative kidney evaluation included renal echography, renal nuclear scan, computed tomography angiography (CTA), and creatinine clearance (CCr). The renal function of the donor kidney was expressed as (donor kidney/both kidneys)%. The percentage renal function from renal echography, renal nuclear scan, and CTA were correlated with CCr. RESULTS: The mean percentage of donor kidney function according to renal echo, nuclear scan, and CTA were 49.77%, 51.83%, and 50.70%, respectively. The correlation coefficients for renal echography, nuclear scan, and CTA to CCr were -0.316, -0.201, and 0.123, respectively. The correlation coefficients for renal echography, nuclear scan, and CTA to postoperative serum creatinine of donor were 0.426, 0.036, and -0.119, respectively. CONCLUSION: From the viewpoint of donor postoperative residual renal function, preoperative renal sonography offered a better predictive value than nuclear scan or CTA.

Silent urothelial cancer detected by sonography after renal transplantation.

OBJECTIVES: Organ transplantation increases the incidence of cancer through unclear mechanisms. In our observation, urothelial cancer happens much more frequently in Chinese people. We reviewed the detection of urothelial cancer in our series after renal transplantation. METHODS: From July 1981 to June 2005, we performed 620 renal transplantations. We do graft and native kidney sonography survey annually even if the patient is asymptomatic. During this period, 10 urothelial tumors were detected. Herein we have reviewed the findings in these cases, along with their management and outcomes. RESULTS: Moderate to severe hydronephrosis of native kidneys was observed in 14 patients, including 9 (64.3%) who had cancer including eight asymptomatic and only one with flank pain and lymph nodes metastasis succumbing in 10 months with a functioning graft. Three patients showed similar degrees of graft hydronephrosis and graft ureteral cancer was diagnosed in one. Mean time from transplantation was 5.09 years. There was a female predominance (7:3). The bladder-to-renal pelvis-to-ureter ratio was 2:5:7, which was distinct from the usual 51:3:1 distribution. In native ureter cancer, we found the left ureter more prone to develop cancer than the right (8:1). CONCLUSION: The pattern of cancer in renal transplant patients is thoroughly different from the general population, namely female predominance, with a higher incidence of ureteral and renal pelvis versus bladder cancer. In our observation, routine periodic sonography survey even in asymptomatic patients is important for urothelial tumor detection, as the incidence of cancer is surprisingly high.

Why we consistently use the left donor kidney in living related transplantation: initial experience of right laparoscopic donor nephrectomy and comparison with left nephrectomy.

OBJECTIVES: Laparoscopic donor nephrectomy has become the method of choice for removal of living donor kidneys. However, the majority of laparoscopic donor nephrectomy cases have been limited to the left side owing to technical difficulties and renal vessel length. This study described the technique and compared donor outcomes and graft function of right and left laparoscopic donor nephrectomy. MATERIALS AND METHODS: Among 25 patients, 6 consecutive donors underwent right laparoscopic donor nephrectomy from March 2002 to January 2005. They were compared to 19 patients with left laparoscopic donor nephrectomy. We compared operative times, warm ischemia times, serial creatinines, creatinine clearances, complications, and graft function. RESULTS: There was no significant difference in any metric. The operative times (303 min. vs 274 min., P > .05) and warm ischemia times (133 s vs 186 s, P > .05) were similar between right and left laparoscopic donor nephrectomy procedures. In left laparoscopic donor nephrectomy, 3 patients had transient brachial plexus neuropathies. No major complication occurred among patients undergoing right laparoscopic donor nephrectomy. This study demonstrated that both donor and recipient outcomes are similar for right and left laparoscopic donor nephrectomy. CONCLUSIONS: Consistent use of the left kidney has not affected clinical outcomes. With hand-assisted laparoscopy, the right laparoscopic donor nephrectomy is safe, providing excellent graft function.

Kidney ultrasound is useful tool in posttransplant follow-up.

OBJECTIVES: Renal sonography has been an important imaging tool in surveys of kidney diseases. We reviewed our experience in the finding and management of asymptomatic patients who underwent renal transplantation. METHODS: We performed baseline graft and native kidney sonography after renal transplantation, as well as annually even if the patient was asymptomatic. At the end of 2004, a total of 326 transplant cases had been annually surveyed. If the findings were positive, they were compared with previous data to determine the need for further examinations and management. RESULTS: The native kidneys of 105 patients were abnormal. Cysts were detected in 71 cases, 23 of which were bilateral. Stones were found in 15 cases. Polycystic kidney disease was identified in 5. The findings in these 91 patients were the same as before. Moderate hydronephrosis was observed in 14 cases. Nine had native ureteral cancer and underwent nephroureterectomy. Ureteral stricture was found in the other 5 patients. Forty-five grafts were abnormal. Thirty-one showed hydronephrosis and 2 underwent ureteral reimplantation. Asymptomatic stones were found in 2. A new single renal cyst was found in 2 cases; and multiple cysts in one other. Elevated RI on color Doppler was discovered in 12 patients, 4 of whom lost their grafts this year. Serum creatinine values of 6.9 and 2.2 mg/dL were observed in 2 patients. CONCLUSIONS: Renal sonography screening is useful not only for the graft but also for the native kidney. Hydronephrosis is an important finding. The high possibility of urothelial malignancy should be expected, requiring further examination and sequential follow-up. Elevated RI is a clue to predict graft outcome; rapid deterioration was observed within months.

Factors Determining Physical and Mental Quality of Life of Living Kidney Donors in Taiwan.

BACKGROUND: Living-donor kidney transplantation has a positive influence on recipients' life expectancy and improves quality of life for patients with end-stage renal disease compared with dialysis patients. Evaluation of the physical and mental quality of life for donors can promote positive perceptions about donation and help potential donors in their decision-making process. The aim of this study was to explore the predictive factors of quality of life for living kidney donors. METHODS: A cross-sectional and descriptive design was used, and the study was conducted from January to July 2013. The donors were a convenience sample of 34 participants who had undergone kidney transplant surgery >1 year earlier. RESULTS: The results showed that kidney donors had a low to moderate physical and mental quality of life. Multiple regression analysis revealed that financial concerns and anxiety explained 27.8% of the total variance of quality of life in the physical component. Anxiety and paid work explained 61.4% of the total variance of quality of life in the mental component. CONCLUSIONS: After renal transplantation, living kidney donors experienced low to moderate quality of life. Because donors are family members (siblings, sons or daughters, spouses, or parents), monthly family income is a significant issue that influences both the decision to donate and quality of life after transplantation. Our findings suggest that pre-transplantation assessment must include social workers as part of the health care team to evaluate the impact of a donor's financial status on post-transplantation quality of life.

Liver stellate cells suppress dendritic cells through IL-10.

Liver allografts can be spontaneously accepted across an MHC class I disparity, the mechanism of which is still not known. Since the liver has a large amount of immature dendritic cells, these elements may contribute to transplant acceptance. However, the reason why liver dendritic cells are immature status is unknown. In this study, bone marrow-derived dendritic cell progenitors were cocultured with liver stellate cells, which produce the immunosuppressive cytokines IL-10 and TGF-beta. The results revealed that dendritic cells cocultured with liver stellate cells express low levels of costimulatory molecules with decreased allostimulatory capacity. Addition of anti-IL-10 antibody to the culture media to neutralize IL-10 effects reversed the allostimulatory function of dendritic cells cocultured with stellate cells. In conclusion, liver dendritic cells are conditioned by stellate cells to maintain an immature status, which may contribute to the low immunity of liver. One of the mechanisms that stellate cells may influence dendritic cells is through IL-10.

Liver-derived dendritic cells induce donor-specific hyporesponsiveness: use of sponge implant as a cell transplant model.

Spontaneously accepted mouse liver allografts are capable of protecting subsequently transplanted donor organs from rejection; however, the underlying mechanisms are unclear. Dendritic cells (DC) residing in liver grafts are likely important in tolerance induction. DC propagated from mouse liver with GM-CSF are phenotypically and functionally immature. They are poor allostimulators in MLR and prolong survival of pancreatic islet allografts. It has been problematic to perform mechanistic studies in an islet transplant model because of difficulties in obtaining sufficient graft infiltrating cells. In this study, we used a sponge allograft model [i.e.. a subcutaneously implanted sponge matrix loaded with B10 (H2b) spleen cells]. To investigate the influence of administration of donor (B10) liver-derived DC on alloimmune reactivity of C3H (H2k) hosts, sponge graft infiltrating cells (SGIC) and recipient spleen cells were isolated, and their immunophenotype and donor-specific cytotoxic T lymphocyte (CTL) activity were examined. The results illustrate that donor-specific CTL activity of T cells are lower in recipients that had received systemic treatment with liver-derived immature DC, associated with a decrease in CD8+ cell population and an increase in Gr-1+ cells in SGIC, compared with recipients treated with mature bone marrow (BM)-derived DC. Interestingly, administration of liver DC directly into the sponge did not inhibit T cell responses. These data suggest that systemic administration of donor liver DC induces donor-specific hyporesponsiveness, probably not by direct inhibition of graft infiltrating T cells. The increased Gr-1+ cells may play immune regulatory roles in induction of host donor-specific hyporesponsiveness.

Is sirolimus a safe alternative to reduce or eliminate calcineurin inhibitors in chronic allograft nephropathy in kidney transplantation?

PURPOSE: We evaluate whether cyclosporine (CsA) or tacrolimus (FK) could be reduced or eliminated after sirolimus was added in chronic allograft nephropathy (CAN). By reducing doses of CsA or FK, we expected that renal function would improve. METHOD AND MATERIAL: Twenty-one patients with CAN had sirolimus added as an immunosuppressive agent. We evaluated the creatinine (Cr) level 3 months after addition. The doses of CsA and FK were decreased gradually and then eliminated over a course of 4 to 6 weeks. If the Cr level rose rapidly or other prominent signs of rejection occurred; low-dose CsA or FK would be added per protocol. We evaluated the duration of engraftment before sirolimus and the Cr level when it was added. RESULTS: Renal function improved in 13 of 21 cases. The improvement in Cr ranged from 12.5% maximally to 1.84% minimally. Seven of 13 cases still required low-dose CsA. The average duration of engraftment before sirolimus was 13.66 +/- 10.80 months. The average Cr level before sirolimus was 1.65 +/- 0.56 mg/dL. In the other eight cases, the Cr level kept rising from 5.1% to 20.4%. The average duration of engraftment was 88.38 +/- 42.21 months. The average Cr level before sirolimus was 2.85 +/- 0.54 mg/dL. Hyperuricemia was noted in 31.3% and hyperlipidemia in 68.8%. CONCLUSION: Sirolimus is a safe alternative to reduce or eliminate CsA or FK in CAN. In cases with a long duration of engraftment and high Cr level, sirolimus might have some effect as a substitute for CNI and thus prevent further nephrotoxicity.