Implementation and Sustainability of European Training Program on Organ Donation in Poland: Results and the Impact on Donation Indicators.

BACKGROUND: Hospital training called ETPOD-Essentials in Organ Donation-was introduced in Poland in 31 hospitals with under-utilized potential of donation. The aim of this study was to assess the effect in hospitals included and not included in program, before and after trainings. METHODS: The number of potential and effective donors, organs used, and number (%) of family refusals were compared at 10 and in 20 months after the training and in equal periods before. RESULTS: In trained hospitals, the number of potential donors increased (17% in 10 months, 10% in 20 months); in remaining hospitals, donors increased in 5% in both periods. In hospitals included in ETPOD, the number of effective donors increased (2% and 4.5%); in the whole country, donors also increased (5.6% and 2.7%). In ETPOD hospitals, the number of utilized organs increased (14.5% and 8.5%); in the rest, the increase was 3% and 7%. In trained hospitals, family refusals increased from 6.9% to 16.2% and from 8.9% to 10.7%; in the whole country, family refusals decreased from 11.7% to 11% in the short term and increased from 9.6% to 12.1% in the long term. CONCLUSIONS: In hospitals involved in the ETPOD program, the increase in organ donation is greater than in the rest of hospitals. Distinct benefit was observed in consent to organ donation.

Evolution of Organ Transplantation in Poland 1966 to 2014: Dates and Numbers.

BACKGROUND: Several events inspired us to collect data on organ transplantation in Poland (2016: the 50th anniversary of the first transplantation and the 20th anniversary of Polish Transplant Coordinating Center Poltransplant). The paper aims at presenting comprehensive data on all organ transplants, beginning with the first in 1966 (deceased kidney) until the end of 2014. METHODS: Source documents were reports published in Poltransplant Bulletin, a website registry managed by Poltransplant, reports by the Transplantation Council and by the Transplantation Institute of Warsaw. A source data enabled us to establish a preliminary report, presented for verification during the 12th Congress of the Polish Transplantation Society. RESULTS: By the end of 2014, the total number of organ transplants was 26,691. Kidney transplantation is the most common (total number = 19,812). The number of living kidney transplants is low, about 50 per year. The number of liver part transplants from living donors is relatively high, 20 to 30 annually. The program of deceased liver transplantation results in more than 300 transplants yearly. The first heart transplantation was in 1985, but the number of these procedures has been decreasing. No significant increase in the number of lung transplantations was noted. CONCLUSIONS: The number of organ transplantations from deceased donors places Poland in the middle among European countries. The number of living donor kidney transplants is lower than in other countries; therefore a living donor liver transplantation program belongs to leading programs. Progress of lung transplantation has been slow. The development is highlighted by vascularized composite tissue transplantations of the hands and face. The strength of the report lies in its reliability and completeness. Numbers are the unique source of information to be used and referred to in the literature.

Increased plasma tissue inhibitors of metalloproteinase concentrations as negative predictors associated with deterioration of kidney allograft function upon long-term observation.

Chronic allograft injury (CAI) is the most frequent cause of progressive kidney allograft impairment and eventual loss, which is due to interstitial fibrosis and tubular atrophy (IF/TA). Mechanisms of CAI are not fully understood. Chemokines, cytokines, metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) play roles in fibrosis development. The aims of this study were to evaluate plasma and urine TIMPs (TIMP-1 and TIMP-2), MMPs (MMP-2 and MMP-9), proinflammatory interleukin-6 (IL-6), chemokine (C-C motif) ligand 2 (CCL2 chemokines previously known as monocyte chemoattractant protein-1 [MCP-1]) among 150 recipients beyond 1 year post-renal transplantations and to explore the usefulness of these potential biomarkers of ongoing allograft injury. Renal transplant recipients compared with healthy volunteers (control group) showed significantly increased plasma and urine IL-6, MMP-9, TIMP-1, and TIMP-2, as well as lower plasma MMP-2 and urine CCL2 concentrations. Compared with recipients showing good function those with impairments displayed higher plasma TIMP-1 (P < .001) and TIMP-2 (P = .003) concentrations. The recipient estimated glomerular filtration rate (eGFR) values negatively correlated with plasma TIMP-1 and TIMP-2 levels (r = -0.43; P < .0001 and rs = -0.42; P < .0001, respectively) and with urine IL-6 excretion (rs = -0.33; P < .0001). Multivariate and receiver operating characteristic (ROC) analyses showed TIMP-1 plasma level assessments to be useful estimates of allograft injury.

Long-term follow-up of non-HLA and anti-HLA antibodies: incidence and importance in renal transplantation.

BACKGROUND: Detection of antibody-mediated injury is becoming increasingly important in post-transplant patient care. The role of donor-specific anti-human leukocyte antigen (HLA) antibodies in kidney transplant damage is known, whereas the significance of non-HLA antibodies remains an unresolved concern. The aim of the study was to determine the presence and influence on renal function of non-HLA and anti-HLA antibodies in stable patients at 5 years after kidney transplantation. METHODS: We evaluated the antibodies in 35 consecutive patients with stable renal function at 5 years after transplantation. RESULTS: Pretransplant screening for donor-specific antibodies by CDC cross-matches was negative in all patients. Anti-endothelial cell antibodies (AECA), anti-angiotensin II type 1 receptor antibodies (anti-AT1R), and anti-endothelin receptor antibodies (anti-ETAR) were assayed as non-HLA antibodies. Non-HLA antibodies were observed in 12 (34%) patients, including AECA (n = 5; 14%), anti- AT1R (n = 6; 17%), anti-ETAR (n = 4; 11%), and both anti-AT1R and anti-ETAR (n = 3). Among 13 (37%) patients with anti-HLA antibodies, 7 also had both non-HLA antibodies: AECA (n = 1), anti-AT1R (n = 3), and anti-ETAR (n = 3). The antibody-negative group (n = 13) showed significantly better renal function than the antibody-positive group (non-HLA and/or anti-HLA; n = 22). Biopsy-proven acute rejection had occurred in 2 of 13 (15%) antibody-negative versus 8 of 22 (36%) antibody-positive patients. These preliminary data revealed an high prevalence of autoantibody and alloantibody production among stable patients at 5 years after kidney transplantation. CONCLUSION: Simultaneous production of these antibodies and their association with reduced renal function suggests that active humoral immune responses are poorly controlled by immunosuppression.

Adventitial lymphatics and atherosclerosis.

Lymphatic vessels are important in reverse cholesterol transport and play a crucial role in regression of atherosclerotic plaque in experimental animal models. Therefore, we attempted to analyze adventitial microcirculation including lymphatic vessels and adventitial macrophages in large human arteries in various stages of atherosclerosis. Eighty-one arterial segments of large arteries (iliac arteries and abdominal aortas) were obtained from deceased organ donors. Lymphatic vessels were identified using anti-LYVE-1 and anti-D2-40/podoplanin immunohistochemical staining. Adventitial blood vessels and macrophages were visualized using anti-CD-31 and anti-CD-68. Intimal thickness was measured under 100x magnification with an Olympus BX 41 light microscope using the visual mode analySIS 3.2 software. Lymphatic vessels were counted in each cross section of the examined arteries, and adventitial blood vessels (CD31+) were counted using the "hot spot" method. Statistical analysis was performed with Statistica 9.1 PL software (StatSoft, Cracow, Poland). Mann-Whitney, F-Cox, Chi-square, and Spearman's correlation tests were performed and the differences were considered significant at p < 0.05. Lymphatic and blood vessels in the adventitia of examined arteries were identified and quantified. Significant positive correlations were found between the number of adventitial lymphatics (LYVE-L +) and intimal thickness (r = 0.37; p < 0.05) as well as with age of the subjects (r = 0.3; p < 0.05). Thus, lymphatic vessels are present in the adventitia of large arteries in humans and the number of adventitial lymphatic vessels increases with progression of atherosclerosis as assessed by intimal thickness.

Duration of brain death and cold ischemia time, but not warm ischemia time, increases expression of genes associated with apoptosis in transplanted kidneys from deceased donors.

Apoptosis is one of the most important mechanisms leading to kidney graft injury during transplantation. The aim of this study was to assess the expression of genes involved in apoptosis in transplanted kidneys derived from deceased donors (DD) at various stages of the transplant procedure, seventy eight transplanted kidneys procured from 43 DD were included in this study. As a baseline control for gene expressions we used six kidney allografts obtained from living donors (LD). Three core biopsies were performed: biopsy 1--5 minutes before organ perfusion in the donor; biopsy 2--at the end of cold ischemia before kidney implantation; and biopsy 3--30 minutes after reperfusion. Tumor protein p53 (TP53), caspase-3 (CASP3), B-cell lymphoma 2 protein (Bcl2), and heme oxygenase 1 (HO-1) gene expression levels were determined using custom-designed low-density arrays (TaqMan assay). Comparison of gene expression between DD and LD kidneys revealed greater expression of all genes in kidneys from DD in all biopsies; however, only CASP3 expression in biopsy 1 and TP53 expression in biopsy 3 were statistically significant. Prolongation duration of brain death beyond 10 hours in DD resulted in a significantly decreased CASP3 expression in biopsy 1. When the cold ischemia time (CIT) was longer than 24 hours, the expressions of Bcl2, TP53, and CASP3 were significantly higher compared to kidneys with ClT<24 hours. There was no correlation between warm ischemia time and gene expression in biopsy 3. CASP3 and TP53 expression only in biopsy 1 were significantly higher among kidney allografts with delayed (DGF) compared with immediate graft function. In conclusion expression of genes involved in apoptosis was more pronounced in kidney allografts from deceased donors. A prolonged donor brain-death period beyond 10 hours resulted in decreased CASP3 expression. CIT longer than 24 hours was associated with increased expressions of Bcl2, TP53, and CASP3. CASP3 and TP53 expressions were significantly higher among kidneys allografts displaying DGF.

Kidney ischemic injury genes expressed after donor brain death are predictive for the outcome of kidney transplantation.

The results of deceased donor kidney transplantation largely depend on the extent of organ injury induced by brain death and the transplantation procedure. In this study, we analyzed the preprocurement intragraft expression of 29 genes involved in apoptosis, tissue injury, immune cell migration, and activation. We also assessed their influence on allograft function. Before flushing with cold solution we obtained 50 kidney core biopsies of deceased donor kidneys immediately after organ retrieval. The control group included 18 biopsies obtained from living donors. Gene expression was analyzed with low-density arrays (Taqman). LCN2/lipocalin-2 is considered a biomarker of kidney epithelial ischemic injury with a renoprotective function. HAVCR1/KIM-1 is associated with acute tubular injury. Comparison of deceased donor kidneys to control organs revealed a significantly higher expression of LCN2 (8.0-fold P=.0006) and HAVCR1 (4.7-fold, P<.0001). Their expressions positively correlated with serum creatinine concentrations after 6 months after transplantation: LCN2 (r=.65, P<.0001), HAVCR1 (r=.44, P=.006). Kidneys displaying delayed graft function and/or an acute rejection episode in the first 6 months after showed higher LCN2 expression compared to event-free ones (1.7-fold, P=.027). A significantly higher increase in expression of TLR2 (5.2-fold), Interleukin (IL) 18 (4.6-fold), HMGB1 (4.1-fold), GUSB (2.4-fold), CASP3 (2.0-fold) FAS (1.8-fold), and TP53 (1.6-fold) was observed among deceased donor kidneys compared with the control group. Their expression levels were not related to clinical outcomes: however, they showed significant correlations with one another (r>.6, P<.0001). We also observed a slightly reduced expression of IL10 (0.6-fold, P=.004). Our data suggested that increased LCN2 and HAVCR1 expression observed in the kidneys after donor brain death were hallmarks of the organ injury process. LCN2 expression level in retrieved kidneys can predict kidney transplantation outcomes.

Extracorporeal photopheresis as an antirejection prophylaxis in kidney transplant recipients: preliminary results.

Extracorporeal photopheresis (ECP) is considered a promising immunomodulatory therapy of acute allograft rejection in organ transplantation and graft-versus-host disease. Our aim was to investigate the biological responses of 10 patients who underwent kidney transplantation with ECP as prophylactic treatment. They received conventional immunosuppressive therapy plus ECP immediately after transplantation: 12 to 16 applications over the course of 2.5 months. ECP procedures were performed using an automated system for leukocyte separation and photoactivation with methoxsalen. All recipients were followed by estimated glomerular filtration rate (eGFR) and peripheral T, B, natural killer, T-regulatory (Treg) and dendritic cells (DC) counts and phenotypes. An acute rejection episode appeared in one control group recipient. The ECP group showed a positive trend to an higher GFR at months 3 (53±11 vs 47.1±9; P=.17) and 6 (67.5±10 vs 53.6±3; P=.03, Wilcoxon test). An increased percentage of Treg (CD3+ CD4+ CD25+) among the total CD3 cell count (4.9%±1% to 9.4%±15%) as well as inducible Treg (CD3+ CD8+ CD28-) was observed among CD3 cells (3.3%±3% to 11.8%±8%, P=.025) within 3 months of ECP treatment. A significant difference in the percentage of Treg was noted at month 3 (completed ECP) between the ECP and the control groups (9.4%±15% vs 3%±1%; P=.01). Addition of ECP to standard immunosuppression was associated with a significantly higher GFR at 6 months and with a significant increase in natural Treg among CD3 cells.

Application of extracorporeal photopheresis in kidney transplant recipients: technical considerations and procedure tolerance.

BACKGROUND: Extracorporeal photopheresis (ECP) is considered to be a promising immunomodulatory therapy in diseases caused by aberrant T lymphocytes. ECP has been used in patients with graft-versus-host disease and systemic scleroderma as well as in solid organ rejection. Herein we report our experience with 148 ECP procedures performed in 10 kidney transplant recipients (12-19 sessions per patient). In 2 subjects, ECP was introduced because of a steroid-resistant rejection episode, and in 8 as supportive treatment in addition to standard immunosuppression in the first 3 months after transplantation. ECP procedures were performed using the UVAR XTS device (Therakos, Exton, PA), an automated closed system for white blood cell separation and photoactivation (ultraviolet light A) with methoxsalen. RESULTS: Vascular access was arteriovenous fistula (n=99), permanent catheter (n=16), peripheral vein (n=25), or polytetrafluoroethylene graft (n=8). Mean blood flow rate was 35.5±5 mL/min. Single ECP procedures lasted 175.5±35 min (range, 120-277), including photoactivation (33.3±30 min). Treatment volume (buffy coat) was 228.4±34 mL per session. Total fluids administered per session were 449.5±60 mL, and mean heparin dose was 5,979±530 IU. ECP-related side effects were transient hypotonia (n=2), increased body temperature (up to 37.5°C; n=4) and red blood cell loss due to a clotted kit or a technical problem with reinfusion (∼100 mL; n=3). CONCLUSIONS: Vascular access for ECP was established in all transplant recipients, using even peripheral veins. Side effects associated with ECP were fairly tolerable by kidney allograft recipients. Caution must be paid to patients with fluid restriction (∼450 mL saline infusion) or the risk of bleeding due to anticoagulation.

Cardiovascular risk in kidney transplant recipients receiving mammalian target of rapamycin inhibitors.

Cardiovascular diseases (CVD) are the leading cause of mortality in renal transplant recipients. Various traditional and unconventional cardiovascular risk factors are potentiated by the adverse effects of immunosuppressive drugs. The mammalian target of rapamycin (mTOR) inhibitors have shown cardioprotective effects in experimental studies, but their influence on CVD in renal transplantation is unclear. The study included 115 kidney transplant recipients treated with mTOR inhibitors with steroids. A group of 38 patients received additionally small doses of calcineurin inhibitor. The control group consisted of 58 kidney transplant recipients randomly chosen among the population of patients transplanted at the same time, who received a calcineurin inhibitor, mycophenolate mofetil or sodium plus steroids. No differences in age, gender, duration of pretransplantat dialysis, time after transplantation, body mass index or glycated hemoglobin existed between the groups. Blood pressure and number of antihypertensive agents, high-density lipoprotein cholesterol, and uric acid levels were similar. The prevalence of diabetic, ischemic, or hypertensive nephropathy as the reason for end-stage renal disease was similar (P=.08). The study group showed higher mean values of total cholesterol (249 vs 204.6 mg/dL; P<.0001) and low-density lipoprotein 136.5 vs 117.7 mg/dL; (P=.015), as well as median values of triglycerides (202 vs 142 mg/dL; P<.0001) and proteinuria (P=.0002). mean estimated glomerular filtration rate was lower in the study group (42.9 vs 51.9 mL/min; P=.0003). Posttransplant diabetes appeared in 38% of the study group compared to 20% of the controls (P=.08). The incidence of coronary artery disease was higher among patients treated with mTOR inhibitors (P=.04). CVD, defined as myocardial infarction, percutaneous coronary intervention, stroke, aortic aneurysm, pulmonary thromboembolism, sudden cardiac death appeared in 26 study group compared with four control patients (P=.24). The risk of any CVD was not significantly higher among patients receiving mTOR inhibitors hazard ratio 1.94; 95% confidence interval 0.83-4.52). In conclusion, no correlation was observed between the duration of mTOR therapy and CVD.

Imbalance of metallaproteinase/tissue inhibitors of metalloproteinase system in renal transplant recipients with chronic allograft injury.

INTRODUCTION: Nowadays, renal allografts continue to be lost at the rate of 2% to 4% per year beyond the first year after transplantation due to chronic allograft injury. Excessive accumulation of extracellular matrix results from overproduction and/or defective degradation by proteolytic enzymes, among which metalloproteinases (MMPs) play a major role. The aim of this study was to assess the role of MMPs in renal transplant recipients (RTR) in the context of allograft injury or proteinuria. MATERIALS AND METHODS: Plasma and urine MMP-2 and MMP-9 and tissue inhibitors of metalloproteinases (TIMPs) were assessed by enzyme-linked immunoassay in 150 RTR including 66% males with an overall mean age of 49.2±11.5 years. The subjects were examined at a mean of 73.4±41.2 months (range=12-240) after kidney transplantation. Thirty-seven healthy volunteers including 54% male with an overall mean age of 48.4±14.1 years served as a control group. RESULTS: Renal transplant recipients displayed significantly decreased plasma MMP-2 activity compared with healthy controls (P<.000) probably due to increased inhibitory plasma (p) TIMP-2 activity (P=.0029), and lower plasma MMP-2:TIMP-2 index (P<.0001). Plasma MMP-9 and pTIMP-1 activities were twofold increased in RTR compared with controls (P=.0015 and P<.000) but with a nearly stable plasma MMP-9:TIMP-1 index (P=NS). There was no difference between RTR and controls according to urine (u) MMP-2 activity, but uMMP-9 was increased in RTR compared with healthy controls (P=.0032). Urine MMP-9 potential was probably diminished by increased uTIMPs (uTIMP-2, P=.017; uTIMP-1, P=.000), which contributed to graft impairment or proteinuria. CONCLUSION: Our study revealed profibrotic MMP/TIMP constellations in RTR that show an imbalance in plasma MMP-2 and MMP-9 with increased plasma and urinary TIMPs. The net proteolytic potential of increased plasma and urinary MMP-9 may be diminished significantly by enhanced plasma and urine TIMP activities.

Does simultaneously transplanted pancreas improve long-term outcome of kidney transplantation in type 1 diabetic recipients?

INTRODUCTION: Simultaneous pancreas-kidney transplantation (SPK) is an alternative to kidney transplantation (KTx) for type 1 diabetic patients with end-stage kidney disease. However, a fair comparison of SPK and KTx is difficult because of significant differences in donor, recipient, and transplantation procedure parameters. The aim of this study was to compare the early and long-term outcomes of SPK versus KTx in southwest Poland. MATERIAL AND METHODS: Thirty-five diabetic dialysis patients who had SPK and 64 patients who had KTx were included in the analysis. RESULTS: SPK recipients were younger (38±6 years versus 42±9 years) and received organs from younger donors (25±7 versus 43±12 years) compared to the KTx group. They had shorter kidney cold ischemia time (9±2 hours versus 22±7 hours) but worse HLA class II mismatches (1.4±0.6 versus 1.0±0.5). In the early postoperative period, three patients died from the SPK group and one patient died from the KTx group. Additionally, two SPK patients lost their pancreatic grafts, and five KTx patients lost their kidney grafts. One-year patient survival rates for the SPK and KTx groups were 88% and 98%, respectively, and 5-year, 81% and 93%, respectively. One-year kidney graft survivals rates for the SPK and KTx groups were 100% and 89%, respectively, and 5-years, 89% and 81%, respectively. One-year insulin-free survival among SPK patients was 90% and the 5-year survival rate was 76%. Excretory function of the transplanted kidneys was better among SPK group; however, the difference reached statistical significance only in posttransplant years 2 and 3: 63.5±20.1 versus 50.3±19.7 and 64.9±12.9 versus 51.6±21.8 mL/min/1.73 m2 for SPK and KTx, respectively. CONCLUSIONS: Normoglycemia in SPK recipients did not improve patient survival at 5 years. The worse HLA compatibility in the SPK group did not lead to impaired kidney graft survival compared to KTx. Better kidney graft function among SPK recipients probably resulted from a more restrictive donor selection.

Hand transplantation--Polish program.

BACKGROUND: Hand transplantations (HTs) are performed in specialized centers proceeding within a board-accepted transplantation program. In Poland such requirements are met by the Subdepartment or Replantation of Limbs of St. Jadwiga Hospital in Trzebnica. The goal of this study was to present the experience of the Center after 3 years of activity. MATERIAL AND METHODS: On creating the "waiting list of would-be hand recipients," we adhered to the inclusion criteria commonly used by other centers. Among 52 potential candidates seen over a 4-year period, the selection process and inclusion criteria yielded 13 patients who were preliminary candidates for an HT. They proceeded to a formal hospital admission to obtain a detailed evaluation including invasive diagnostic tests. The group consisted of 12 men of age 21-42 years with single dominant hand amputations and 1 woman of 23 years with amputations of both hands. Within this group we performed 3 HTs in 3 men of 32, 42, and 30 years old: 2006 and in 2007 at mid-forearm level and in 2008 at the distal forearm level. The times elapsed from amputation to HT were 14, 6, and 7 years, respectively. RESULTS: The first patient achieved total motion of fingers equal to 63% of that of his unaffected hand. Evaluation using the SF-36 protocol gave a result of 50; by DASH, 95; by CFSS (according to Lanzetta and Petruzzo), 84 (excellent). He had only 1 mild rejection episode. Our second HT failed. The third patient has a good hand function, namely, 80% of the finger motion of the unaffected hand and sensitivity reaching his finger tips. No rejection episodes were observed. CONCLUSION: On the basis of these results, we plan to proceed with the hand transplantation program.

1,25-dihydroxyvitamin D deficiency predicts poorer outcome after renal transplantation.

OBJECTIVE: To assess 1,25-dihydroxyvitamin D status and the effect of vitamin concentration on transplantation outcome in renal allograft recipients. PATIENTS AND METHODS: Ninety patients underwent renal transplantation between 2002 and 2005. All received alfacalcidol supplementation before surgery. 1,25-Dihydroxyvitamin D concentration was determined on day 3 posttransplantation and at 1-, 6-, 12-, 18-, and 24-month follow-up. RESULTS: Severe 1,25-dihydroxyvitamin D deficiency was noted in 83% of patients immediately posttransplantation. From 1 to 12 months thereafter, concentrations increased almost 3-fold, and remained constant to 24 months. In 50% of patients, the 1,25-dihydroxyvitamin D concentration reached a concentration of more than 30 pg/mL, similar to that in healthy volunteers; in the other 50%, the concentration reached 17.2 pg/mL. A high incidence of delayed graft function was observed in patients with 1,25-dihydroxyvitamin D deficiency (44% vs 6%). There was a negative correlation between the initial 1,25-dihydroxyvitamin D and serum creatinine concentrations at day 3 and month 6 (P < .03). Similarly, the 1,25-dihydroxyvitamin D concentration at 1 month was negatively correlated with creatinine concentration at months 1 through 24 (P < .01). Poor outcome was observed primarily in patients with 1,25-dihydroxyvitamin D deficiency; 2 patients developed cancer, 5 grafts were lost, and 4 patients died of cardiovascular events. CONCLUSIONS: 1,25-Dihydroxyvitamin D deficiency is highly prevalent in renal allograft recipients. Patients with 1,25-dihydroxyvitamin D deficiency are at greater risk of delayed graft function, and the graft is more likely to be lost. These findings suggest the necessity of adequate vitamin D supplementation both before and after transplantation.

Pretransplantation cellular alloreactivity is predictive of acute graft rejection and 1-year graft function in kidney transplant recipients.

OBJECTIVE: To study cellular alloimmunity in kidney allograft recipients using an interferon-gamma enzyme-linked immunosorbent spot assay (ELISPOT). MATERIAL AND METHODS: Donor splenocyte peripheral blood mononuclear cells were obtained during kidney recovery in 53 kidney recipients including 11 with positive panel-reactive antibodies pretransplantation. For ELISPOT data analysis, the spot number, size, and intensity were calculated, reflecting the volume of cytokine secretion at the single-cell level. Results were recalculated as the ratio of the values observed for donor-stimulated to unstimulated recipient cells corrected for residual donor activity. RESULTS: Significantly greater pretransplantation donor-stimulated activity was observed in recipients who experienced an acute rejection episode (ARE) within 1 year (P < .05). Mean change in spot number, size, and intensity in patients without or with AREs was 0.99 vs 3.33, 1.60 vs 6.05, and 1.40 vs 6.31, respectively. The assessed parameters were prognostic of high risk of ARE: 1.5-fold increase in spot number (ARE incidence, 52% vs 9%), 2.5-fold increase in spot size (ARE incidence, 53% vs 13%), and 2.7-fold increase in spot intensity (ARE incidence, 52% vs 9%). The 3 parameters correlated with 1-year serum creatinine concentration (P < .05). In 14 recipients, AREs could have been predicted in 11 using pretransplantation ELISPOT results, and in only 2 on the basis of panel-reactive antibodies. CONCLUSION: The ELISPOT-determined capacity of donor-induced reactivity observed in recipient cells obtained just before transplantation is predictive of risk of graft rejection and 1-year allograft function.

Estimated glomerular filtration rate evolution between 6 and 24 months predicts long-term kidney transplant survival among patients with inferior graft function.

UNLABELLED: One-year serum creatinine and other clinical and immunologic factors remain uncertain predictors of long-term kidney allograft outcomes. The aim of our retrospective study was to evaluate the prognostic significance of the estimated glomerular filtration rate (eGFR) monitoring of patients with suboptimal kidney allograft function. The analysis included 332 patients (median age, 43 years), who received deceased donor kidney transplantations between 1995 and 2007 with graft function for at least 1.5 years (median follow-up, 7 years). We examined the eGFR (the 4-variable Modification of Diets in Renal Disease [MDRD] equation) at 6 month posttranspant and every 6 months thereafter. Based on eGFR stratification (>60, 50-60, 40-49, and <40 mL/min per 1.73 m(2)) at 6 months we divided the patients into 4 groups. We identified patients with eGFR improvement (as judged by >20% increment between 6 and 24 months), versus stable or declining eGFR courses. RESULTS: Among the groups, the eGFR improved among 47% of patients. Demographic characteristics including time on dialysis, human leukocyte antigen matching, cold ischemia times were similar across groups. A greater incidence of disadvantageous characteristics was observed among the deteriorating groups: older donor, higher delayed graft function incidence, as well as more frequent and severe acute rejection episodes. Excellent and comparable 5-year graft survivals were noticed among patients with improved eGFR between 6 and 24 months (97%, 100%, 100%, 94%). CONCLUSION: Assessment of eGFR was a valuable biomarker for long-term kidney transplant outcomes among patients with inferior renal transplant function. A tendency to improve eGFR between 6 and 24 months posttransplant was advantageous for graft survival, possibly indicating state of immunologic quiescence.

Evolution of bone disease at 2 years after transplantation: a single-center study.

Posttransplant bone disease is caused by renal osteodystrophy. We sought to examine bone mineral density (BMD) among 90 renal allograft recipients of mean age 42.7 +/- 11.4 years to identify factors preventing bone loss at 2 years posttransplant. Subjects treated with cyclosporine or tacrolimus plus azathioprine/MMF and prednisone underwent BMD estimates of the lumbar spine (LS) and of the proximal femur using dual energy x-ray absorptiometry (DEXA) at 3 months and every 6 months for 2 years. We assayed markers of bone remodeling: intact parathyroid hormone (iPTH), calcitriol, osteocalcin, and carboxyterminal telopeptide of type I collagen on day 3, as well as month 1 and every 6 months after transplantation. At the initial measurement, we observed osteopenia (OSP) among 35% in the LS and 52% in the femur: there was osteoporosis in 8.3%. The prevalence of OSP increased during the first year, thereafter decreasing to the initial value, but the rate of osteoporosis did not change significantly (8.3% vs 6.0%). BMD and Z-score decreased during the first and increased in the second year; 27% of patients regained initial values and 38% higher ones. BMD gains in the LS and femur were observed among subjects with higher calcitriol levels during the first 6 months (P < .01), higher osteocalcin (P < .05), higher estimated glomerular filtration rate during 1-24 months and in the tacrolimus group. Improvement of LS BMD occurred in younger patients (38 vs 46 years; P < .027); BMD gain in the femur correlated with higher levels of iPTH from 1-12 months (P < .01). The tacrolimus group showed higher Z-scores in the LS and femur at 24 months (P < .05). Two years after transplantation >60% of recipients showed stabilization or gain in bone mass. A sufficient calcitriol level in the early transplant period, an adequate iPTH, good renal function, and tacrolimus therapy prevented BMD disease progression.

A detailed comparison of the functional outcome after midforearm replantations versus midforearm transplantation.

OBJECTIVES: The functional outcome after midforearm transplantation (HT) is believed to be similar to the outcome after replantation. However, the few existing reports comparing functional outcomes are based on amputations at the level of the distal forearm. This report provides a comparative analysis of the functional results after midforearm replantation (HR) versus HT. MATERIALS AND METHODS: Transplantation of a dominant right forearm performed in a 32-year-old man was compared to the outcomes after five dominant (right) forearm replantations (four men and one woman) in patients ranging from 22 to 38 years of age. Cold ischemia time ranged from 6 to 12.5 hours in all cases. We used similar operative technique and rehabilitation protocol. At 26 (+/-2) months after replantation/transplantation, we recorded, bony union (x-ray), arterial flow (ultrasonography), range of motion, grip strength, sensation (2 PD Weisensten's filaments), quality of life (DASH, 30-150 points), general evaluation of function according to Chen's or the IRHCTT scoring system. RESULTS: A complication of wound infection was observed in one HR patient; Marginal skin necrosis accompanied by prolonged wound healing, in one HT patient. Unification of bones was achieved faster after forearm replantation when compared with transplantation. Grip strength was 17% greater after replantation, but ranges of motion were comparable in both groups. Sensitivity was superior after forearm transplantation (2 PD 15 mm) and overall patient satisfaction was comparable (90 points of DASH questionnaire for HR versus 108 points for HT patients). None of the patients returned to their previous occupations. CONCLUSION: The functional outcome after HT was comparable, and in some respects superior, to the outcome after replantation performed at the midforearm level.

First Polish forearm transplantation: report after 17 months.

INTRODUCTION: The number of hand transplantations is increasing every year prompted by promising results. Still, the number of transplantations performed at the level of midforearm/elbow is relatively small. The aim of the study was to evaluate after 17 months postoperatively the result of the first Polish upper limb transplantation performed at midforearm level. MATERIALS AND METHODS: The transplant recipient was a 32-year-old man, who lost his right, dominant upper limb at the level of midforearm in an accident 14 years prior. After a comprehensive pretransplantation evaluation and informed consent process we transplanted a right forearm matched for size and skin tone from a 47-year-old brain-dead man. The donor's limb amputated at the elbow was irrigated with University of Wisconsin solution. We dissected donor and recipient limbs simultaneously. The cold ischemia time was 10.5 hours. Immunosuppression included Simulect, tacrolimus, mycophenolic acid, and prednisone. Maintenance therapy included tacrolimus, mycophenolic acid, and Encorton. RESULTS: There were no intraoperative or early postoperative complications, except for delayed wound healing. No episodes of rejection were observed. Immunosuppression was well tolerated. In the process of physiotherapy, a continuous passive motions device was applied, as well as special tests to stimulate tactile sensation. After 11 months, Tinel's sign reached the finger pulps innervated by the ulnar nerve and after 12 months, by the median nerve. The monofilament test/Semmens-Weinstein was positive after 17 months: blue for ulnar nerve and purple for median nerve. The sensations proved grade 3+ and grade 3, respectively. The activity of intrinsic muscles was not detectable by electromyography; active range of motion included 63% of the unaffected hand. The extremity excellently matched the contralateral hand for size, color, and skin texture. The patient uses his hand for writing, riding his bike, and a mobile phone. The total Lanzetta' score was excellent (82 points).

Mild rejection episode evoked by modification of immunosuppressive protocol observed in a patient with forearm transplantation: case report.

Skin is the most immunogenic component of a composite tissue allograft (CTA). Clinicopathologic monitoring of the skin seems to be the most reliable method to detect rejection in CTA patients. The symptoms in cases demonstrating full-blown rejection are clear, contrary to those of just mild rejection. The aim of the study was to present the symptoms of mild rejection observed in a midforearm transplant patient at 20 months postoperative. The 32-year-old man underwent right dominant forearm transplantation at 12 years after a traumatic amputation. During the first 20 months, the course was uneventful, with no signs of impaired function. Immunotherapy at 20 months consisted of: Cellcept (2 g/d), prednisolone (10 mg/d), tacrolimus (7 mg/d; level C(0) of 13 ng/mL), An attempt was made to modify therapy by diminishing the tacrolimus dose to 4 mg/d (C(0)-8 ng/mL). After 10 days postimplementation of the new regimen, are hardly visible macullopapular erythematous rash appeared on the palmar and dorsal sides of the hand as well as the skin of the forearm. There was a slight red swelling of the nail bed margins. No deterioration of hand function was observed. The patient was immediately admitted to the hospital; despite unclear clinical and pathomorphological symptoms, we diagnosed a mild rejection (grade I). The therapy consisted of methylprednisolone (500 mg three times daily for 3 consecutive days) and 5 days of topical application of immunosuppressant ointments (tacrolimus and Protopic) with maintenance of the previously applied oral tacrolimus doses. After 5 days of treatment, the symptoms subsided. This approach utilized the advantage of the unique possibility to treat rejection locally, consistent with current awareness that skin is the primary target of hand rejection. However, topical application of immunosuppressants has not been extensively investigated. The manifestations of rejection in CTA patients may be heterogeneous and difficult to diagnose.