Post-transplant lymphoproliferative disorder in adult renal transplant recipients: case series and review of literature.

Post-transplant lymphoproliferative disorder (PTLD) is serious life-threating complication of transplantation. The clinical picture differs from lymphomas observed in the general population, with different manifestation, histopathology, higher aggressiveness with involvement of sites beyond the primary lymph node, and poorer outcome. The objective of the study was to present nine cases of PTLD observed in our centre among the kidney transplant recipient population and discuss the results with up-to-date literature. We performed a retrospective single-centre assessment of PTLD incidence in the cohorts of kidney transplant recipients followed by our centre. We found nine cases of PTLD, five men and four woman, aged from 26 to 67 years at the time of diagnosis (mean [SD] 48 [5] years), transplanted between 1997 and 2013. The disease was diagnosed between 2002 and 2017, from 6 to 440 months after transplantation (mean [SD] 96 [137] months). A diffuse large B-cell lymphoma was found in seven cases early as well as late after transplantation, and two patients presented T-cell lymphoma. Five patients achieved complete remission with no relapses after 6 to 13 months of treatment. In three cases the remission was achieved by switching to mammalian target of rapamycin inhibitors (mTORi) only. Four recipients died from 2 weeks to 15 months after PTLD was diagnosed. Although the diagnostic criteria of different forms of PTLD are commonly known, rapid and correct diagnosis is not easy. PTLD is a relatively a rare disease, so there are too few studies and little consensus on the optimal treatment.

Immune activation- and regulation-related patterns in stable hand transplant recipients.

We assessed cell subsets and expression of a set of genes related to the T-cell populations in peripheral blood mononuclear cells to elucidate whether immune status of stable hand transplant recipients (HTx) differs from stable kidney transplant recipients (KTx). The study was conducted on five HTx 4.8 ± 1.7 years after transplantation and 30 stable KTx 7.9 ± 2.4 years after transplantation as well as 18 healthy volunteers. The research involved PBMC gene expression analysis of CD4, CD8, CTLA4, GZMB, FOXP3, IL10, IL4, ILR2A, NOTCH, PDCD1, PRF1, TGF-B, and TNF-A genes on a custom-designed low-density array (TaqMan) as well as flow cytometry assessment of lymphocyte subpopulations. HTx presented significantly increased expression of immunomodulatory genes (TNF, IL10, GITR, and PDCD1) compared to KTx and controls. HTx revealed a proinflammatory molecular pattern with higher expression of NOTCH and CD8 compared to KTx and controls. KTx showed a reduced level of regulatory T cells compared to controls and HTx. Both HTx and KTx presented an increased number of CD8+ and CD8+ CD28- T cells compared to controls. Stable hand transplant recipients exhibit persistent immune activation with rejection-related gene expression pattern counterbalanced by secondary induction of regulatory mechanisms.

Immunoregulatory role of B lymphocytes in alloresponse to kidney transplant.

B cells are a group of diverse phenotype and function subsets, which can both stimulate and inhibit the immune response to an allograft. They participate in the rejection process by influencing differentiation, proliferation and effector functions of T lymphocytes. B cells injure the graft via the ADCC (antibody-dependent cellular cytotoxicity) reaction and humoral rejection through plasmocyte production of donor-specific antibodies. A converse, suppressive mode of B cells can attribute to the development of tolerance and protect the graft from rejection. This function is provided by the regulatory B cells, which negatively control the immune response by producing suppressor cytokines (IL-10, IL-35, TGF-ß), natural antibodies and through cellular interactions. In effect they inhibit the development of Th1 and Th17 effector cells, and induce differentiation of regulatory T cells. Operational immune tolerance in human kidney transplant recipients was associated with increased number of naïve and transitional B cells of regulatory function, and increased gene expression for differentiation of B cells. However, in chronic alloantibody transplant rejection the distorted distribution and function of regulatory B cells was found, which implies their pivotal role in graft tolerance. Currently, the immunosuppressive regimens unselectively inhibit the activity of T and B cells, by interfering with their effector and immunoregulatory functions. They do not fully control the chronic rejection reaction, which is the major cause of graft loss. Comprehension of the mechanisms of immunologic homeostasis dependent on B cells can help develop immunosuppressive protocols targeted at tolerance.

Pretransplant Immune- and Apoptosis-Related Gene Expression Is Associated with Kidney Allograft Function.

Renal transplant candidates present immune dysregulation, caused by chronic uremia. The aim of the study was to investigate whether pretransplant peripheral blood gene expression of immune factors affects clinical outcome of renal allograft recipients. Methods. In a prospective study, we analyzed pretransplant peripheral blood gene expression in87 renal transplant candidates with real-time PCR on custom-designed low density arrays (TaqMan). Results. Immediate posttransplant graft function (14-day GFR) was influenced negatively by TGFB1 (P = 0.039) and positively by IL-2 gene expression (P = 0.040). Pretransplant blood mRNA expression of apoptosis-related genes (CASP3, FAS, and IL-18) and Th1-derived cytokine gene IFNG correlated positively with short- (6-month GFR CASP3: P = 0.027, FAS: P = 0.021, and IFNG: P = 0.029) and long-term graft function (24-month GFR CASP3: P = 0.003, FAS: P = 0.033, IL-18: P = 0.044, and IFNG: P = 0.04). Conclusion. Lowered pretransplant Th1-derived cytokine and apoptosis-related gene expressions were a hallmark of subsequent worse kidney function but not of acute rejection rate. The pretransplant IFNG and CASP3 and FAS and IL-18 genes' expression in the recipients' peripheral blood is the possible candidate for novel biomarker of short- and long-term allograft function.

The influence of non-HLA antibodies directed against angiotensin II type 1 receptor (AT1R) on early renal transplant outcomes.

Non-HLA antibodies (Abs) targeting vascular receptors are thought to have an impact on renal transplant injury. Anti-angiotensin II type 1-receptor-activating antibodies (anti-AT1R) have been mentioned to stimulate a severe vascular rejection, but the pretransplant screening has not been introduced yet. The aim of our study was to assess the incidence and importance of anti-AT1R antibodies and their influence on renal transplant in the 1st year of observation. We prospectively evaluated the presence of anti-AT1R antibodies in 117 consecutive renal transplant recipients in pre- and post-transplant screening. Anti-AT1R antibodies were observed in 27/117 (23%) of the analyzed recipients already before transplantation. The function of renal transplant was considerably worse in anti-AT1R(+) group. The patients with anti-AT1R Abs >9 U/ml lost their graft more often. Biopsy-proven AR was described in 4/27 (15%) pts in the anti-AT1R(+) group and 13/90 (14.4%) in the anti-AT1R(-) group, but more severe cases of Banff IIB or antibody-mediated rejection (AMR) were more often observed in anti-AT1R (+) 4/27 (15%) vs. 1/90 (1.1%) in anti-AT1R(+) (P = 0.009). Patients with anti-AT1R Abs level >9 U/ml run a higher risk of graft failure independently of classical immunological risk factors. The recipients with anti-AT1R Abs developed more severe acute rejections described as IIB or AMR in Banff classification. More recipients among the anti-AT1R-positive ones lost the graft. Our study suggests monitoring of anti-AT1R Abs before renal transplantation for assessment of immunologic risk profiles and the identification of patients highly susceptible to immunologic events, graft failure, and graft loss.

[The evaluation of cost-effectiveness and cost-utility of valganciclovir for the prophylaxis of cytomegalovirus disease to 200 days after kidney transplantation]. / Ocena kosztowej efektywnosci i kosztowej uzytecznosci stosowania walgancyklowiru w profilaktyce wystapienia choroby cytomegalowirusowej do 200. dnia od przeszczepu nerki.

UNLABELLED: Standard procedure for cytomegalovirus disease (CMV) prophylaxis in kidney transplant patients was the administration of valganciclovir for up to 110 days after organ transplant. This prophylaxis has been extended up to 200 days in Poland since 2011. The decision was based on the results of clinical trials which showed significant clinical benefit in case of prolonged administration of the drug. The aim of the analysis was to provide the economic evaluation of extending the CMV prophylaxis with co-financed from public funds Valcyte (valganciclovirum; 60 tab. a 450 mg; Roche Polska Sp. z o.o.) from 110 to 200 days, in the high risk patients group after kidney transplant (seronegative recipient and infected donor, D+/R-). The analysis was performed from the Polish healthcare payer's perspective. MATERIAL AND METHODS: All methods used in the following study were consistent with the Requirements of the Polish HTA Agency (AHTAPOL). The cost-effectiveness and the cost-utility analysis were performed on the basis of a randomised study which was identified as a result of the systematic search of the medical databases, comparing 200 days valgancyclovir administration with 100 days drug use as a prophylaxis of CMV disease in the patients group mentioned above. The Markov model was developed, simulating the disease evolution over time considering a high risk patient after kidney transplant treated with valgancicloviras the CMV disease prophylaxis. The disease period was divided into health states that are the most probable for this condition and the transitions probabilities between them were identified and assigned. Based on the clinical trial results, registry database of health conditions usability and experts' opinion, all health states (i.e. death, kidney transplant, CMV disease) were attributed with utilities and costs. The direct costs, important from the Polish healthcare payer's perspective, were included in the analysis. Extension of the proposed model in the series of one month time cycles made it possible to assess long-term (assumed time horizon was median patient's life expectancy--23,5 years) costs and clinical effects of the compared technologies. RESULTS: The Incremental Cost-Effectiveness Ratio (ICER) was 39 669 008 PLN and The Incremental Cost-Utility Ratio (ICUR) was 48 008 PLN in the specified time horizon. The result is well below the accepted threshold of profitability in Poland (assuming tripled GDP per capita cost-utility threshold, i.e. 99 543 PLN), which means that the therapy is cost-effective. CONCLUSIONS: The results of the analysis confirmed that the 200 days use of valganciclovirin the prevention of CMV disease compared to standard 110 days therapy is economically justified from the Polish healthcare payer's perspective.

Assessment of Global Longitudinal Strain in Patients Receiving Renal Replacement Therapy With Preserved Left Ventricular Ejection Fraction.

BACKGROUND: Patients with chronic kidney disease, including those on renal replacement therapy (RRT), have higher cardiovascular mortality. Global longitudinal strain (GLS) detects subtle changes in the left ventricle (LV) and constitutes a more sensitive predictor of cardiovascular mortality than the LV ejection fraction (LVEF). The aim of this study was to assess the prevalence of impaired GLS among patients on RRT with preserved LVEF. We also aimed to identify the possible clinical factors responsible for GLS impairment. METHODS: A total of 108 patients on RRT with preserved LVEF and no history of cardiac disease were evaluated. We assessed echocardiogram parameters with a calculation of GLS, laboratory parameters, presence of diabetes, hypertension, duration of hemodialysis (HD), and the time after kidney transplantation (KTx). An impaired GLS value was set at ≥-18%. The multivariate stepwise logistic regression analysis was used to identify the factors related to impaired GLS. RESULTS: Among 108 patients aged 58.5 ± 13.5 on RRT with preserved LVEF, 45% had GLS ≥-18% (62% on HD, 39% after KTx). The ROC analysis revealed that the cutoff point for the predicted GLS ≥-18% by HD duration was more than 28 months (0.75 [95% CI 0.66-0.84]; P < .001). In multivariate stepwise logistic regression analysis, a duration of HD longer than 28 months was associated with GLS ≥-18%. CONCLUSIONS: About 45% patients on RRT, despite preserved LVEF and no history of heart diseases, had LV systolic dysfunction defined as GLS ≥-18%. HD longer than 28 months significantly increases the risk of GLS impairment in patients on RRT.

The Global Longitudinal Strain in Renal Transplant Recipients and Immunosuppressive Regimen.

BACKGROUND: Echocardiographic global longitudinal strain (GLS) has recently been considered as a more effective assessment than the ejection fraction (EF) in detecting subtle changes of left ventricular (LV) systolic function. The aim of the study is to compare GLS in renal transplant recipients (RTrs) with preserved LVEF, depending on the recipient's immunosuppressive regimen. The impaired GLS was considered to be > -18%. METHODS: A total of 84 RTrs were divided into 2 groups depending on immunosuppressive regimen: group 1, which included 32 patients (aged 62.3 ± 7.5) receiving mammalian target of rapamycin inhibitors, and group 2, which included 52 patients (aged 58.9 ± 13.9 treated with calcineurin inhibitors. In all patients, echocardiography was performed, including calculation of GLS, and laboratory and clinical markers of cardiovascular risk were assessed. RESULTS: The frequency of men was significantly higher in group 1 (P = .01). There were no differences between the groups in age, body mass index, frequency of diabetes, hypertension, time of hemodialysis (HD) before kidney transplantation (KTx), time after KTx, concentration of cholesterol and creatinine, echocardiographic linear parameters, and LV mass. The estimated glomerular filtration rate and triglyceride concentration were significantly higher in group 1. The mean value of GLS was similar in both groups (-19.8 [-3.5] vs -18.9 [-3.0]; P = .22). The multivariate logistic regression analysis revealed that duration of HD > 26 months is associated with GLS ≥ -18% (odds ratio 2.95, 95% CI 1.08-7.99, P = .03) CONCLUSIONS: The frequency of impaired GLS in RTr was similar regardless of the type of the immunosuppressive regimen. The impaired GLS was associated with duration of HD before KTx.

[Resistin: a pathogenic factor or a biomarker of metabolic disorders and inflammation?]. / Rezystyna--czynnik patogenetyczny czy biomarker zaburzen metabolicznych i zapalenia?

Cardiovascular diseases are currently the most frequent cause of death in Poland and their incidence continually rises. This is related to the high incidence of obesity associated with insulin resistance, which is present in type 2 diabetes mellitus. Adipose tissue produces multiple cytokines(TNF-alpha, IL-6, PAI-1, CRP, angiotensinogen, leptin, adiponectin, visfatin, apelin, resistin)which decrease insulin sensitivity and induce inflammatory processes, endothelial dysfunction,and atherosclerosis. This article presents the link between obesity, insulin resistance, and type 2 diabetes mellitus according to studies conducted in vitro and in animal models. In human studies, the influence of resistin on the development of insulin resistance is controversial. The article underlines the role of resisitin in the development of inflammatory processes and endothelial dysfunction in humans. In clinical studies, resistin was shown to be a predictive factor of coronary artery disease and mortality connected with cardiovascular diseases.

Transforming growth factor-beta1 gene expression and cyclosporine A-induced gingival overgrowth: a pilot study.

AIMS: The relationship between gingival overgrowth (GO) induced by cyclosporine A (CsA) and transforming growth factor-beta1 (TGF-beta1) remains unclear. The aims of the present study were to evaluate TGF-beta1 gene expression under different immunosuppressive treatments and its association with TGF-beta1 gene functional polymorphism and GO in renal transplant recipients. MATERIAL AND METHODS: The study included 98 CsA-treated renal transplant recipients (with and without GO) and 44 tacrolimus-treated transplant patients (without GO). TGF-beta1 mRNA expression was measured using a real-time quantitative polymerase chain reaction assay. The levels were correlated with TGF-beta1 gene polymorphisms at codons 10 and 25, with different immunosuppressive treatment and GO. RESULTS: The level of TGF-beta1 gene expression was insignificantly lower in the CsA-treated group compared with the tacrolimus group, and significantly lower in the group with GO compared with patients without GO. In tacrolimus- and CsA-treated patients, but not in patients with GO, the level of TGF-beta1 gene expression was associated with functional phenotypes of TGF-beta1. The incidence, degree and extent of GO were higher in recipients with lower TGF-beta1 gene expression. CONCLUSIONS: Lower level TGF-beta1 gene expression, not functional polymorphism, in patients treated with CsA may be considered to be a risk factor for GO.

Anti-Fya antibodies as the cause of an unfortunate post-transplant course in renal transplant recipient.

BACKGROUND: Duffy glycoprotein, belonging to blood group alloantigens, is also recognized as chemokine-binding protein, therefore the role of Duffy antigen in chemokine distribution has been postulated. Duffy positive phenotype prevalent among Caucasians is associated with antigen expression on erythrocytes and endothelium of several organs including kidney. The role of anti-Duffy antibodies significant in transfusiology may be also important in kidney transplantation. CASE REPORT: The case of renal transplant recipient with Fy (a-b+) phenotype, possessing anti Fya antibodies, with unfortunate post-transplant course complicated with acute cellular and antibody-mediated graft rejections, with the presence of crescentic glomerular lesions, kidney graft insufficiency and recurrent urinary tract infections is presented. The role of anti-Duffy antibodies in acute antibody-mediated rejection is discussed. CONCLUSIONS: Fy(a )antibodies present in renal recipient with Fy(a-b+) phenotype may be the reason for unfavorable transplantation outcome resulting from reaction against Duffy antigen up-regulated on graft tissue during ischemia reperfusion injury and acute rejection episode. In renal transplant recipients with antibody-mediated rejection without antidonor specific antibodies, incompatibility in blood group antigens other than AB0 system could be considered.

Impact of sirolimus treatment in kidney allograft recipients with prolonged cold ischemia times: 5-year outcomes.

OBJECTIVES: Sirolimus, an effective and non-nephrotoxic immunosuppressant, may have an antiproliferative effect on renal tubular cells and increase their apoptosis, thus hindering the recovery of an injured kidney. The aim of this study was to evaluate the impact of combined sirolimus and cyclosporine therapy on the incidence and duration of delayed graft function and long-term graft function. MATERIALS AND METHODS: The study group consisted of 23 renal transplant recipients treated with a sirolimus-cyclosporine-prednisone regimen (sirolimus group). The reference group was composed of 23 patients treated with azathioprine-cyclosporine-prednisone. Because of a long cold ischemia time, all the patients were at high risk of developing delayed graft function. RESULTS: There was an equal frequency of delayed graft function in the sirolimus group compared with the reference group (39% vs 34.8%). The duration of delayed graft function was longer in sirolimus group compared with the reference group (21.2 +/- 12.2 days vs 6.8 +/- 2.5 days) (P < .004). The serum creatinine level at the 12th month was higher in patients with delayed graft function than it was in the remaining patients, independent of the immunosuppression protocol. One and 5-year graft survival rates were 100% and 87% in the sirolimus group, and 95% and 74% in the reference group. The 5-year patient survival rate was 100% in both groups. CONCLUSIONS: Sirolimus significantly retards the recovery from posttransplant renal failure, but it does not increase the incidence of delayed graft function. Sirolimus therapy should be initiated after recovery from posttransplant renal failure. Sirolimus treatment is beneficial for long-term graft survival.

Aortic root dilation in kidney transplant recipients.

INTRODUCTION Aortic root (AoR) dilation is associated with cardiac damage and higher cardiovascular risk. Cardiovascular disease is the most common cause of death in patients after kidney transplantation (KTx ). OBJECTIVES The aim of this study was to assess the prevalence of enlarged AoR diameter in KTx recipients. Patients with bicuspid aortic valve, significant valvular disease, or evidence of connective tissue disorder were excluded. PATIENTS AND METHODS A total of 87 KTx recipients were divided into 2 groups depending on immunosuppressive regimen: 41 patients receiving mammalian target of rapamycin inhibitors (mTORi) and 46 patients treated with calcineurin inhibitors (CNIs). In all patients, echocardiography was performed, laboratory and clinical markers of cardiovascular risk were assessed, and the AoR diameter was calculated. RESULTS There were no differences between groups in age, sex, body surface area, body mass index, frequency of diabetes, hypertension, dyslipidemia, time after replacement therapy, creatinine levels, and estimated glomerular filtration rate. In the CNI group, the observed and calculated AoR diameters were similar (P = 0.8). In the mTORi group, the observed AoR diameter was higher than the calculated one (P = 0.002). The concentric and eccentric left ventricular hypertrophy was similar in both groups (P = 0.12 and P = 0.69, respectively). In the stepwise regression analysis, the AoR diameter was associated with body surface area and mTORi treatment. CONCLUSIONS KTx recipients have a high prevalence of AoR dilation. Immunosuppressive regimen based on mTORi increases the incidence of AoR enlargement.

Reccurence of Kaposi's sarcoma after increased exposure to sirolimus.

UNLABELLED: The conversion to sirolimus treatment is recently indicated as an effective therapy of Kaposi's sarcoma (KS) in transplant patients. We present two treatment modalities in patients with KS and recurrence of the disease after increasing sirolimus dose. Among 1034 renal transplants performed at our center, three (0.3%) suffered from KS. Initial immunosuppression consisted of cyclosporine, azathioprine and prednisone in one patient; and tacrolimus, mycophenolate mofetil and prednisone in two patients. KS symptoms appeared within one year post-transplantation. Two patients developed cutaneous tumor; one disseminated disease, including the skin, mediastinal lymph nodes and both lungs. After histological confirmation of KS immunosuppression was minimized: Two were converted to sirolimus (1-2 mg/day, level 5-8 ng/ml) treatment; the third patient discontinued tacrolimus and was administered 1 g/day mycophenolate mofetil. Gradual regression of KS was observed in all the patients. In one patient, 8 months after regression of lung KS, the dose of sirolimus was increased to 2 mg/day (level raised to 13.8 ng/ml). Recurrent disease developed afterwards involving diffuse interstitial infiltrates with nodular changes in both lungs. For the second time the dose of sirolimus was reduced to 1 mg/day (level 4-5 ng/ml) and lung lesions regressed 5 months later. Renal function was stable (creatinine 1.3-1.9 mg/dl) in all patients, 24 months from KS onset. IN CONCLUSION: treatment by low sirolimus or mycophenolate mofetil doses caused regression of KS. Recurrence of KS after increasing sirolimus dose suggests that regression of KS is a result of diminished immunosuppression, not the direct antineoplastic effect of sirolimus. Careful maintenance of low sirolimus levels is suggested.

The relationship of transforming growth factor-beta1 gene polymorphism, its plasma level, and gingival overgrowth in renal transplant recipients receiving different immunosuppressive regimens.

BACKGROUND: Cyclosporin A (CsA) induces gingival overgrowth (GO) in patients who seem to be prone to this disorder. It is still impossible to determine which patients will develop GO. Patients treated with the new immunosuppressive drug tacrolimus seem not to have GO. The aims of this study were to investigate transforming growth factor-beta1 (TGF-beta1) gene polymorphisms in renal transplant recipients treated with CsA or tacrolimus and to establish an association between these polymorphisms and TGF-beta1 plasma concentration and the incidence of GO. METHODS: The examined group consisted of 134 renal transplant recipients. Ninety-two underwent CsA treatment (50 with and 42 without GO), and 42 underwent tacrolimus treatment. Age, gender, time after transplantation, calcineurin inhibitor total dosage, number of teeth, and sulcus bleeding index were analyzed. TGF-beta1 plasma levels were estimated in 60 CsA- and 30 tacrolimus-treated patients. Two biallelic polymorphisms of the TGF-beta1 gene were studied at codon 10 (at position +869) and at codon 25 (at position +915) in patients from the examined group and in 108 healthy volunteers (the control group). RESULTS: The distribution of the high, intermediate, and low TGF-beta1 producer phenotypes was comparable in all the studied groups and in the healthy controls. The high producer phenotype was more frequent in patients with GO. TGF-beta1 levels in the CsA group showed correlation with the phenotypes. The lowest incidence of GO was observed in the 10C/C genotype, whereas the highest was observed in the 10T/C genotype. CONCLUSION: High and intermediate TGF-beta1 producer phenotypes and heterozygous genotype 10T/C might be considered risk factors for GO in patients treated with CsA.

Conversion from cyclosporine-based immunosuppression to tacrolimus/mycophenolate mofetil in patients with refractory and ongoing acute renal allograft rejection.

AIM OF THE STUDY: was to examine the influence of conversion from cyclosporine-based therapy to tacrolimus/mycophenolate mofetil (MMF) on renal graft survival in patients with refractory rejection and on the recurrence of rejection in patients converted at the time of the first episode of rejection. PATIENTS AND METHODS: A total of 64 renal graft recipients were converted to tacrolimus/MMF: 30 patients (Group I) in whom acute allograft rejection was not resolved after anti-rejection therapy; 34 patients (Group II) with first acute rejection, in whom tacrolimus/MMF was an adjunctive therapy to corticosteroid treatment. RESULTS: In Group I, ten patients failed to recover graft function. Another 10 patients lost their grafts within 2 years after conversion. Two-year graft survival was 30%. Gastro-intestinal complications or leucopenia necessitated immunosuppressants dose reduction or interruption in 50% of the patients. In Group II, recurrence of acute rejection episode occurred in 12% of patients. Ten patients (30%) developed chronic rejection within 2 years after conversion. One and two year kidney graft survival was 97% and 93.6% respectively. CONCLUSIONS: Conversion to tacrolimus/MMF in patients with refractory rejection improved or stabilized renal function, but this effect was short-lasting. Intolerance of immunosuppressive drugs contributed greatly to the treatment inefficacy. Conversion to tacrolimus/MMF during the first acute rejection resulted in low risk of recurrent rejection. Nevertheless, progression to chronic graft nephropathy was observed.

[Biopsy eosinophilia as a predictor of renal graft dysfunction]. / Naciek eozynofilowy w biopsji jako czynnik prognostycny dysfunkcji przeszczepionej nerki.

Effector cells such as eosinophils and mononuclear cells play crucial role in the mechanism of injury during acute renal allograft rejection (ARAR). The aim of the study was to evaluate an influence of tissue eosinophilia observed in the renal allograft biopsy (RAB) during ARAR on rejection severity (reversibility) as well as long-term graft function. The histopathological examination and the quantitative assessment was performed in 165 RAB with symptoms of ARAR. The numbers of eosinophils were counted at high power (40xobj), over the entire renal cortex, minimum 10 high power fields(hpf). Results. Significant tissue eosinophilia was found in 49 RAB (29%). In the Eosinophilic Group (EG) we observed: more frequent biopsy-confirmed ARAR episodes (1.79 vs. 1.33/pts; p=0.03), higher grade of acute rejection according to the Banff classification (p=0.007), more severe clinical course of rejection expressed as worse graft function at 6 month after treatment (serum creatinine 2.2 vs. 1.5 mg/dl). Chronic rejection was seen in 25% pts of EG and in 11% pts of Control Group (CG) in the first year after Tx. Graft survival at 6 month in the EG was shorter then in the CG (91% vs 96.3%). Conclusions. Eosinophilic infiltration of RAB is a negative predictor, which can indicate more severe course of ARAR and increased resistance to an anti-rejection therapy. It can determine an appearance of chronic allograft dysfunction hazard.

[Mycophenolic acid concentration profiles may select recipients with high-risk of acute rejection in renal transplant recipients]. / Przydatnosc pomiarów stezenia kwasu mykofenolowego w osoczu w okresleniu zagrozenia wystapieniem ostrego odrzucania u biorców przeszczepu nerki.

UNLABELLED: The aim of the study was to assess relationship between the pharmacokinetics of mycophenolic acid (MPA) and the risk of developing acute rejection within 6 months after renal transplantation. MATERIAL AND METHODS: MPA concentrations were measured using validated HPLC. Venous blood samples for assay of MPA plasma concentrations were evaluated before (trough level; C) and 40 minutes, 1, 2 and 4 hours after mycophenolate mofetil (MMF) oral administration. The study included adult kidney cadaveric graft recipients: 26 patients treated with CsA, MMF and prednisone. MPA AUC was determined using the linear trapezoidal rule. Statistical significance was assessed using ANOVA Statistica. RESULTS: A total of 13 patients experienced biopsy proven rejection. Patients with acute rejection had lower GFR, lower serum albumin and were younger. There was statistically significant difference for MPA AUC(0-4), C40, C(max) between patients with acute rejection and patients with uneventful outcomes: mean MPA AUC(0-4): 11,4 +/- 7,23 microg x h/ml versus 34,0 26,8 microgxh/ml (p 0,01). Recipients with MPA AUC(0-4) <20 g x h/ml had a greater risk of acute rejection. CONCLUSIONS: MPA AUC(0-4) was a useful predictor of outcome in renal recipients within first 6 months after renal transplantation.

Transplantology: Challenges for Today.

Clinical transplantology in Poland had its 50th anniversary this year. With the early and long results comparable to the best achieved in the world leading centers, we face old and completely new challenges for this medical speciality. Main and growing challenge is insufficient number of available organs. With less than 15 donors/mln population/year Poland stay in the lower row of European countries in this measurement of transplant activity. Donation system is not efficient enough and we lose a big number of potential donors still. Living donation (with the exception for the fragments of the liver) remains low despite of different initiatives made so far on the national and local levels. Donation after cardiac death is possible from the point of Polish juridical regulations, but since last 3 years had not showed real impact on country donation rates (only three procedures done). Methods of tissue typing remain slow and cause relatively long times of cold ischemia for kidney programs. Second main challenge is chronic rejection causing loss of organs in the long-term follow-up and no efficient treatment employed. The emerging possibility of tolerance induction despite of plenty of new protocols proposition in the publications does not show up a clinical everyday practice in work. The same is with xenotransplantation promises; even we were informed recently that till 2030 such genetically modified porcine organs will be available. The next challenge is production of organs and tissues from own recipients cells installed on the different scaffolds or 3D printed. Other challenge is the personnel working in this field. We observe like in the other European countries lack of new candidates for work in this field together with serious problems of nursing staff, being a catastrophic perspective in country medical service in general, not only in transplant centers. The last but not least challenge is financial side of transplant programs.

Beneficial effect of bilateral native nephrectomy as complete denervation on left ventricular mass and function in renal transplant recipients.

INTRODUCTION: Left ventricular hypertrophy (LVH) is a risk factor for cardiovascular morbidity and mortality in renal transplant recipients. The development of LVH is connected with excessive activation of the sympathetic nervous system. A bilateral nephrectomy is an example of complete renal denervation. OBJECTIVES: The aim of this study was to evaluate the effect of pretransplant bilateral native nephrectomy on left ventricular mass and function during a long-term follow-up of patients after kidney transplantation. PATIENTS AND METHODS: The study group consisted of 32 renal transplant recipients who had previously undergone pretransplant bilateral native nephrectomy. The control group involved 32 recipients with preserved native kidneys, matched for age, sex, creatinine levels, estimated glomerular filtration rate, immunosuppressive treatment, and the time of renal replacement therapy. All patients were evaluated by echocardiography, and 16 patients--by cardiac magnetic resonance (CMR). In addition, all patients had their arterial blood pressure (BP) and metabolic markers measured. RESULTS: In comparison with controls, the study group had lower systolic BP (P = 0.048) and received a lower number of antihypertensive agents (P = 0.001). Lipid and hemoglobin levels were similar in both groups. The study group had a lower left ventricular mass index (LVMI; P = 0.001) and left atrial volume index (LAVI; P = 0.004). The left ventricular mass evaluated by CMR was also lower in the study group (P <0.001). Mild left ventricular diastolic dysfunction (LVDD) was more frequent in the study group compared with the control group ( P <0.001). CONCLUSIONS: In a long-term follow-up of patients after kidney transplantation, the bilateral native nephrectomy before transplantation was associated with a lower LVMI and LAVI as well as a lower grade of LVDD. These patients had lower systolic BP and used fewer antihypertensive drugs.