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Introduction: Hypertension is diagnosed in over 50% of renal transplant patients, and its presence is associated with significantly increased risk of cardiovascular complications. The pathogenesis of hypertension in this group of patients is complex. The use of immunosuppressive drugs is among the most important risk factors due to their hypertension-inducing properties. It is also suspected, that fatty acids may play an important role in the development of the disease; however, the mechanism of its formation has not yet been fully elucidated., Aim: Evaluation of fatty acid profile in phospholipids fraction in the blood serum of patients after renal transplantation, with respect to the blood pressure and immunosuppressive drug used., Materials and Methods: The study included 65 kidney transplant patients treated with immunosuppressants: 24 patients received CsA (9 women, 15 men) and 41 were treated with Tac (15 women, 26 men). Blood pressure level was estimated by taking an average value of the last 3 measurements in an outpatient setting. Blood pressure exceeding 140/90 mmHg was considered as abnormally high. The number of antihypertensive drugs administered was based on the analysis of patients’ records and direct interviews with patients. The concentration of each fatty acid was determined using gas chromatography. Statistical analysis was performed using Statistica 10., Results: There were no statistically significant differences between both: systolic blood pressure (136.16 vs. 133.31 mmHg, p=0.499) and diastolic blood pressure (80.62 vs 80.76; p=0.962) in patients treated with CsA compared to those taking Tac. Patients treated with CsA, received – on average – more antihypertensive drugs, compared to the group of patients taking Tac (2.64 vs 2.17), but this difference was also not statistically significant (p=0.174). The profile of fatty acids in renal transplant recipients treated with CsA was similar in both with normal blood pressure and with elevated blood pressure. In case of patients treated with Tac, significantly lower concentrations of C14 (p=0.015), C16:1 (p=0.039), C18:1 (p=0.043) and MUFA (monounsaturated fatty acids; p=0.049) were found in patients with higher values of blood pressure, compared to the ones whose blood pressure was within the norm. A significantly higher concentration of fatty acids: C14 (p=0.029), C16:1 (p=0.049) and C20:5 (p=0.029) was found in patients with normal blood pressure, treated with Tac as compared with treated with CsA. In contrast, regardless to the immunosuppressive drug used, no statistically significant differences were found between the patients’ groups with elevated blood pressure values., Conclusion: The prevalence of hypertension in renal transplant recipients treated with CsA and Tac is similar. The fatty acid profile in phospholipids fraction depends on the blood pressure and the immunosuppressant used.

Unlabelled: The C4d urinary excretion seems to increase with the risk of graft rejection or progression of chronic allograft nephropathy although its impact on long-term kidney transplant (KTx) outcomes remains unclear. Presently the most common maintenance immunosuppression schemes (IS) includes corticosteroids and cyclosporine or tacrolimus (Tac) with mycophenolane mophetil (MMF), and Tac combined with MMF is regarded to be superior to other schemes. The aim of the study was to determine whether the initial (1-3 months post KTx) level of C4d urinary excretion may help to predict long-term kidney allograft transplantation outcomes in patients treated with Tac+MMF as maintenance IS., Material and Methods: The study involved 66 patients who had undergone kidney allograft transplantation. The urine specimens taken from the morning urine portion was assessed by ELISA test for C4d excretion. To increase the objectivity of the assessment all measurements were divided by urinary creatinine excretion (ng/mgCr). The study population was grouped according the calculated Roc curve (the cut off value of the urinary C4d excretion 13.1 ng/mgCr; AUC 0.93; 95% CI 0.74-0.95) into LC4d and HC4d, C4d below or above 13.1 ng/mgCr., Results: The mean C4d urinary excretion was 166.6 +/- 186.3 ng/mL (3.9 +/- 6.2 ng/mgCr), in LC4d and HC4d 34.8 +/- 102.2 ng/mL (1.1 +/- 6.4 ng/mgCr) and 347.3 +/- 255.7ng/mL (19.2 +/- 5.9 ng/mgCr), respectively. In accord with the division of study population, the statistically significant differences were seen between LC4d and HC4d in urinary C4d excretion Z = 4.4; p = 0.019 (Z = 4.9, p = 0.011 for excretion calculated per urinary creatinine). Kaplan-Meier curve analysis demonstrated a higher graft survival rate in LC4d than in HC4d group (p = 0.048 by log-rank) in ten years follow-up., Conclusions: In patients treated with tacrolimus and mycophenolate mophetil as a maintenance immunosuppression, the lower C4d urinary excretion in the early post-transplant period seems to be a low significance prognostic marker of a better long-term kidney allograft transplantation outcome.

Unlabelled: The aim of the study was to evaluate the influence of the type of prescribed immunosuppression: cyclosporine A (CsA) vs. tacrolimus (Tac) on remote homocystein levels in patients (pts) after kidney transplantation (Ktx)., Patients and Methods: The study included 51 pts (17 F, 34 M) aged 15 to 62 years (mean 38.1) after cadaver Ktx. The mean observation period equaled 21.2 months (6 -24); while total observation period was 90 personlyears. Before Ktx, 46 pts were treated with maintenance hemodialysis (HD), while 5 by peritoneal dialysis (PD). After Ktx, patients had immunosuppression prescribed according to the following schemes: prednisone (P) + CsA + azathioprine (AZA) - 12 pts; P + CsA + mycophenolate mofetil (MMF) -26 pts; P + Tac + MMF - 11 pts; and P + Tac + AZA - 2 pts. Hcy level was measured using high performance liquid chromatography (HPLC). Serum creatinine level was measured by standard method using the Hitachi 917 analyzer. Creatinine clearance was calculated based on the Cockcroft-Gault formula. Patient's blood was drawn before Ktx and 3, 6, 9, 12,15, 18, 21 and 24 months post procedure., Results: Delayed graft function (DGF) after Ktx was diagnosed in 29 pts (56.9%) and this group required from 4 to 28 HD sessions (mean 14 sessions). Hcy level did not significantly differ between pts requiring (29 pts) and not requiring (22 pts) HD treatment after Ktx. It was also noted that the number of performed HD sessions did not significantly correlate with Hcy levels 24 months after Ktx (R =0.04, p=0.81). No relationship was found (non-parametric Spearman test) between the drop in Hcy level 3 months after Ktx as compare with value before Ktx and ischemia time (R=0.09, p=0.49), number of compatible HLA A and B (R=0.07, p=0.63), and DR antigens (R=0.09, p=0.51). Decrease in Hcy level (before Ktx and 24 months after Ktx) did not significantly correlate with the above parameters, respectively: R=-0.14, p=0.40; R=0.06, p=0.73; R=0.12, p=0.45; R=0.11, p=0.50. Decrease in Hcy level (before Ktx and 3 months after) did not differ significantly when compared to pts receiving immunosuppressive therapy CsA vs. Tac (p=0.18). Even though notable differences were observed in the drop in Hcy level (immunosuppressive treatment scheme CsA vs. Tac) in measurements before Ktx and 24 months post (respectively: 27% and 57.6%), no statistical significance was noted (p=0.13). Using the Mann-Whitneys' Test, no statistical significance was noted (p=0.13) when comparing differences in creatinine clearance between the group of pts receiving CsA and Tac 24 months after Ktx. Patients treated with Tac achieved a higher creatinine clearance by 16.5% when compared with those receiving CsA. No significant differences were observed between these two groups (p=0.65) when serum creatinine levels were evaluated., Conclusions: Incidence of DGF, as well as prescribed immunosuppressive therapy does not have an influence on remote Hey levels in pts after Ktx. Graft function seems to be the main predictor that influences Hcy levels after Ktx in this group of pts.

Oxidative stress causes disturbances in homeostasis leading to an excessive production of reactive oxygen species (ROS). Free-radical reactions undergo intensification during transplantation and are responsible for both damage to the graft and cardiovascular complications, one of the major causes of patient death. The function of immunosuppressive drugs in this process is currently the object of research. Investigations of medications which would decrease the level of oxidative stress are in progress. Tacrolimus (FK-506) is a medication commonly used in immunosuppressive therapy. It has a better cardiac-lipid profile than cyclosporine A. Some reports about the beneficial effect of tacrolimus on the level of oxidative stress in the organism have appeared. Especially in vitro studies and animal tests indicate antioxidative properties for tacrolimus. Decreases in parameters of oxidative stress, such as the concentration of malone dialdehyde (MDA), the activity of myeloperoxidase (MPO), and neutrophilic infiltration, were observed after treatment. In in vitro studies on endotheliocytes, tacrolimus induced oxidative stress more weakly than other medications and was the only one that did not increase the production of nitric oxide (NO). The protective effect of tacrolimus on inflammatory response in rat liver during ischemia-reperfusion injury, on atrocytes exposed to stimulated ischemia in vitro, and in experimental traumatic injury of spinal cord tissues in rats were also described. Findings in patients after transplantation are not so clear and even indicate that the influence of tacrolimus on the activity of antioxidative enzymes in kidneys may be involved in side-effect of tacrolimus.

Modem immunosupressive agents have greatly reduced incidence and severity of acute renal allograft rejection. One-year graft survival rate of 95% can be easily achieved with optimal immunosuppressive regimens. However, long-term kidney transplant survival has improved poorly. At present, chronic allograft nephropathy (CAN) and recipients death (mainly due to circulatory complications, neoplasms and infections) are most common reasons of graft loss in the second and subsequent years after transplantation. Moreover adverse effects of immunosuppressive drugs (nephrotoxicity, arterial hypertension, dyslipidaemia, post-transplant diabetes mellitus) can account for development of CAN. Regimens with combination of at least two drugs are administered to recipients, as it allows for using minimal effective doses and reduces the risk of adverse effects. Narrow therapeutic window of most immunosuppressive agents forces clinicians to adequately monitor serum concentration of the drug or its metabolite. Early postransplant period requires higher doses, which then are reduced. Immunosuppressive regimen is individualized, to minimize the risk of acute rejection, but also to avoid overimmunosuppression and its complications. Presently there are two trends in immunosuppressive schemes: first one to withdraw glycocorticosteroids and the other one to reduce dose or withdraw calcineurin inhibitors, mostly because of their nephrotoxicity.