Vitamin D Concentration in Patients After Heart and Kidney Transplantation.

BACKGROUND: One of the main actions of vitamin D is bone mineralization regulation. Vitamin D is linked also to hypertension, diabetes, and cardiovascular disease. Vitamin D deficiency may result in osteomalacia, but its excess may result in bone calcium mobilization. Kidney transplant recipients are also at risk of hypovitaminosis D because of impaired graft function. The aim of the study was to assess vitamin D concentration in patients after heart and kidney transplantation. MATERIAL AND METHODS: Ninety-eight stable heart transplant recipients were enrolled in the study; 80 kidney transplant recipients and 22 healthy volunteers served as controls. The laboratory tests, including parameters of 25-hydroxyvitamin D (calcidiol), were assayed using commercially available kits. RESULTS: Calcidiol deficiency (level below 10 ng/mL) was observed in 10% of the transplant group and in 55 % of the orthotopic heart transplant recipients (OHT). There was positive correlation between calcidiol concentration, hemoglobin, kidney function, and serum glucose in kidney transplant recipients. In OHT, vitamin D correlated with age, kidney function, hemoglobin, cholesterol, low-density lipoprotein cholesterol, and glucose. Both groups had similar kidney function. In both groups of patients with estimated glomerular filtration rate above 60 mL/min/1.72 m2, vitamin D was significantly higher. In OHT, vitamin D was higher in nondiabetic patients. In OHT in multivariate analysis, vitamin D was predicted in 24% by kidney function (beta = -0.30; P = .02) and hemoglobin concentration (beta = 0.25; P = .03). CONCLUSIONS: Vitamin D deficiency is more common in patients after heart transplantation than in kidney allograft recipients despite similar kidney function. The possible associations between the cardiovascular system and vitamin D merit further studies.

Kallistatin Concentration and Hypertension in Heart Transplant Recipients.

Development of arterial hypertension is to some extent related to decreased activity of the kallikrein-kinin system. This poorly understood hormonal system consists of blood proteins playing a role in the process of inflammation, coagulation, blood pressure control, and pain conduction. The system consists of kallikreins (plasma and tissue), kallistatin, kininogens, kinins (bradykinin, kallidin-lizynobradykinin), kininases (I and II), and membrane receptors of bradykinin. The aim of the study was the assessment of kallistatin in correlation to blood pressure value in heart transplant recipients. PATIENTS AND METHODS: Kallistatin level was estimated in 131 heart transplant recipients on standard 3 drugs immunosuppressive regimens (calcineurin inhibitor, mycophenolate mofetil/mycophenolic acid, and steroids) in correlation to inflammation markers and blood pressure values. Additionally, 22 healthy volunteers served as controls. In cross-sectional study, kallistatin and catecholamine concentrations were assessed using commercially available assays. RESULTS: Kallistatin concentration did not differ significantly among heart transplant recipients in comparison with controls; serum noradrenaline concentration was lower in the study group. In the orthotopic heart transplant group, kallistatin correlated with renal function; estimated glomerular filtration rate was calculated by Modification of Diet in Renal Disease formula (r = -0.28, P < .01; hemoglobin r = -0.19, P < .05; cholesterol level r = -0.23, P < .01; low-density lipoprotein r = 0.25, P < .01; ferritin r = 0.21, P < .05; noradrenaline r = -0.28, P < .01). No correlation with blood pressure values were revealed. In multivariate analysis, cholesterol serum level and age predicted 32% of variability of kallistatin concentration. CONCLUSION: Kallistatin among heart transplant recipients does not seem to be the pathogenetic factor of arterial hypertension but may be involved in the development of hyperlipidemia often present in this group of patients.

Opinions and Attitudes of Medical Students About Organ Donation and Transplantation.

BACKGROUND: Although transplantation has gained more support and acceptance, there are still many ethical, moral, and legal barriers associated with this form of treatment. The demand for organs is higher than what can be accommodated. Current medical students are forming their views about transplantation. METHODS: The aim of this study was to investigate the perspectives of 569 students from the Faculty of Medicine, Medical University of Bialystok, Poland, with regard to their beliefs about organ donation. RESULTS: Respondents included in this study were 21.77 ± 2.03 years of age (73.6% female, 80.1% living in an urban setting). Organ procurement and transplantation from living donors was found to be acceptable by 97.54% of respondents, and 98.77% found deceased donor procurement to be acceptable. More than 90% of respondents agreed with organ donation from family members after death, and agreed to donation after their own death. However, only 54.77% indicated an agreement to donate in their lifetime for nonrelatives. It was found that 70.74% believe the final decision on cadaveric organ donation should be made by the family. A positive attitude toward organ transplantation was expressed by 96.47% of respondents, but 2% submitted an objection to placement on a central registry. Refusals for organ donation included emotions associated with death (88%), religious beliefs (42%), and lack of knowledge of medical terminology (24.78%). According to respondents, the concept of transplantation should be managed by patients and donors (65.38%), universities (49.56%), or the media (44.64%). CONCLUSION: Medical students generally agree on procurement of organs from deceased and living donors. However, their enthusiasm for organ donation after death diminished with regard to their family members. An educational campaign promoting organ transplantation should be considered.

Future Lawyers Support Organ Donation and Transplantation.

In 2016 the total number of solid organ transplantations in Poland was 1469; the number of patients on waiting lists was approximately 1600 every month, and demand for organs is increasing every year. Transplantation has achieved increasing support and acceptance among Polish people; however, there are still many ethical, moral, and legal barriers related to this form of treatment of end-stage organ failure. MATERIAL AND METHODS: The research method is a diagnostic survey of 347 law students from the Faculty of Law, University of Bialystok, Poland. The research tool was the authors' questionnaire. RESULTS: Responders were 21.172 ± 1.34 years old (67.4% female, 74.4% urban residence). Organ procurement and transplantation from living donors are accepted by 95.6% of respondents; 97.4% are accepted from deceased donors. More than 80.4% of the respondents would agree to organ donation from their family members after death and to be donors after their death. The majority of students (80.1%) believe that the final decision of deceased organ donation should be made by the family. Despite positive attitude towards transplantation (97%), about 2% have submitted their objection to the central registry. Refusal of organ donation was associated mainly with emotions related to death (89%) and religion (47.6%). According to responders, the transplantation should be managed by patients and donors (42.1%) and universities (31.7%). CONCLUSIONS: Law students generally accept procurement of organs from deceased and living donors, but in situations related to family members, their acceptance rates drop significantly. According to future lawyers, patients, donors, and universities should educate society about issues related to organ transplantation.

Eye Problems in Patients on the Active and Inactive Kidney Transplantation Waiting List.

Renal transplant is the best form of treatment for most patients with end-stage renal disease. The aim of this study was to examine the prevalence of eye problems in patients with end-stage renal disease on the kidney transplantation waiting list in regard to their status (active vs temporarily disqualified). The cross-sectional study was conducted on 90 prevalent patients in 1 regional qualification center. There were 24 peritoneally dialyzed patients, 5 patients registered for preemptive transplantation, and 61 hemodialyzed patients. Average age of patients who had been registered on the cadaver kidney waiting list was 50 (± 14) years, with a balanced sex ratio and median dialysis duration of 38 months. The primary cause of end-stage renal failure was chronic glomerulonephritis in 42 cases, diabetic nephropathy in 10 cases, hypertensive nephropathy in 12 cases, autosomal dominant polycystic kidney disease in 7 cases, and other or unknown in the remaining patients. The major diagnosis was hypertensive angiopathy (related to the presence of long-term hypertension and history of kidney disease) in 56 patients, diabetic retinopathy in 8 patients, blindness in 4 cases (due to solvent intoxication in 1 case), and eyesight abnormalities (myopia, hyperopia, anisometropia) in 7 cases. Cataracts were described in 10 patients in addition to other findings. In 15 patients ophthalmology examination was normal, predominantly in younger patients. Abnormalities were more common in patients on the inactive list. In the vast majority of potential kidney transplant recipients, ophthalmology disturbances are primarily related to the underlying disease. The ophthalmology consult is part of the qualification, but the abnormalities are not the exclusion criteria.

Endocan Concentration in Kidney Transplant Recipients.

INTRODUCTION: Endocan is a novel soluble dermatan sulfate proteoglycan derived from endothelium. It has the capacity of binding to different biologically active molecules associated with cellular signaling, adhesion and regulating proliferation, differentiation, migration, and adhesion of different cell types in health and pathology. Elevated endocan levels are connected with endothelial activation/damage, neo-angiogenesis, and inflammation or carcinogenesis. MATERIALS AND METHODS: The level of serum endocan among 63 kidney transplant recipients on three immunosuppressives (calcineurin inhibitors, mycophenolate mofetil, steroids) in correlation with other markers of endothelial damage was estimated. Additionally, 22 healthy volunteers were studied. Using a cross-sectional study design, the markers of endothelial damage like endocan, von Willebrand factor (vWF), intracellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM); markers of inflammation high-sensitivity C-reactive protein (hsCRP) and IL-6; and marker of kidney function cystatin C were measured using commercially available assays. RESULTS: Endocan, vWF, IL-6, hsCRP, ICAM, and VCAM levels were significantly higher in kidney transplant recipients comparing to healthy volunteers. In kidney transplant recipients, endocan levels correlated with renal function (estimated glomerular filtration rate by Modification of Diet in Renal Disease, r = -0.24, P < .05, creatinine r = 0.26, P < .05), time after transplantation r = -0.24, P < .05, activity of aspartate aminotransferase r = -0.46, P < .001, alanine aminotransferase r = 0.34, P < .01), ICAM r = -0.53, P < .001, VCAM r = -0.34, P < .01, hsCRP r = 0.35, P < .01, IL-6 r = 0.28, P < .05, vWF r = 0.26, P < .05. In a multifactorial analysis, the predictors of endocan levels were creatinine, ICAM, and VCAM predicting 59% of variability. CONCLUSION: Endocan concentration among kidney transplant recipients is potentially connected with endothelial damage dependent upon graft function and time after transplantation.

Underrecognition and Underestimation of Disturbances in Calcium-Phosphate Balance in Kidney Transplant Recipients.

Disturbances in mineral metabolism, namely chronic kidney disease-metabolic bone disease, became more profound with impairment of renal function. The aim of the study was to assess how often calcium, phosphate, alkaline phosphatase, and parathyroid hormone (PTH) were measured in kidney transplant recipients relative to hemodialyzed patients. In addition, prevalence of hypercalcemia defined as calcium concentration over 10.5 mg/dL was assessed. PATIENTS AND METHODS: We studied 200 kidney allograft recipients and 100 hemodialyzed patients. Calcium, phosphate, alkaline phosphatase, 25-hydroxy vitamin D, and PTH were obtained from outpatient charts. RESULTS: All the studied parameters were available in 100% of the hemodialyzed patients. In kidney allograft recipients, calcium and phosphate levels were available in 80%, alkaline phosphatase activity was available in 40%, PTH was available in less than 10%, and vitamin D was available in 1%. Hypercalcemia was present in 10% of hemodialyzed patients and in 5% of kidney allograft recipients. Vitamin D analogue was administered to 98% of hemodialyzed patients, whereas vitamin D was administered to 28% of kidney allograft recipients, particularly those with impaired kidney function. In conclusion, calcium and phosphate are seldom assessed on an outpatient basis in kidney allograft recipients, making the diagnosis and treatment of secondary hyperparathyroidism in this population difficult. Care of kidney transplant recipients could be substantially improved, particularly in regard to chronic kidney disease-metabolic bone disease, when regular check-ups for calcium-phosphate balance are implemented and proper treatment could be introduced to prevent further chronic kidney disease-metabolic bone disease.

Do Age and Religion Have an Impact on the Attitude to Organ Transplantation?

BACKGROUND: Religious issues may be a significant reason for the lack of organs for transplantation. Younger people have a more enthusiastic attitude toward organ donation. The goal of the present study was to determine whether age and religion affect people's attitudes to organ transplantation. METHODS: This trial was a diagnostic poll study using an original survey questionnaire involving 1273 people living in Podlaskie Voivodeship. RESULTS: Treatment with the use of organs from dead donors was approved by 88.3% of the respondents aged ≤60 years and 70.5% of those aged >60 years; the highest number of those who opposed this procedure occurred in the group aged >60 years (22.3%). Baptists approved of the method more often than persons of other religions; Muslims disapproved of it more often than others (25%). Approximately 96% of the participants, regardless of religion, had a positive attitude toward organ transplantation, but only 81% aged >60 years had a positive attitude toward organ donation; there were significantly more Catholics in this group (P < .026). In the group aged >60 years, 63.8% expressed their consent; 66.7% of them were Muslims and Baptists. Approximately 86% of persons aged ≤60 years were willing to donate their own organs after death. These people were significantly more often Catholic (P < .045). CONCLUSIONS: Age and religion have a considerable influence on positive attitudes toward transplantation. The majority of younger people, as well as Catholics, approve of the removal of organs from living donors and from dead donors.

Opinions and Attitudes of University Students Concerning Organ Transplantation.

INTRODUCTION: Organ donation and transplantology are receiving more and more support and approval all over the world every year. However, there remains a considerable and growing difference between the number of patients awaiting transplantation and the number of donors. The aim of the work was to find out the opinions and attitudes of university students concerning organ donation and transplantology. MATERIAL AND METHODS: Our poll surveyed 405 students from 2 universities (Medical University of Bialystok [MU] and Bialystok University of Technology [UT]). The research tool used in the study was an original survey questionnaire. RESULTS: Treatment with the use of organs taken from living persons was approved by 55.6% of the students, from dead donors, by 73.6%, and 1.2% of the participants did not approve of that way of treatment. Of the students from the MU, 84% approved the removal of organs from close relatives after their death; 79.5% of those from the UT approved. Of the UT students, 8% were against the removal of organs from close relatives after their death; 4% of MU students were against it. Of MU students 94.5%, would agree to have their own organs removed after death; 85.3% of UT students would agree. Of MU students, 54.2% of students had informed their families about their will to have organs removed; 29.4% of UT students had informed their families. A greater number of medical students had a declaration of will (28.9% vs 13.2%; P < .001). The kind of university had a significant (P = .002) influence on the students' attitudes to transplantation. A positive attitude was displayed by 94.5% of MU students and 83.8% of UT students, whereas a negative one, by 2% of UT students and 0.5% of MU students. CONCLUSIONS: Different degrees of knowledge and acceptance of organ donation were manifested by university students. To a great extent, this depended on the kind of university. MU students understood the topic and approved of the treatment to a greater degree. A permanent educational campaign should be carried out among young people, especially those studying at universities other than medical.

Prospective Assessment of Hepcidin in Relation to Delayed or Immediate Graft Function in Patients Undergoing Kidney Transplantation.

BACKGROUND: Hepcidin is a peptide hormone that regulates iron homeostasis. Hepcidin may represent an early, predictive biomarker of acute kidney injury, another model of ischemia-reperfusion injury. Urinary hepcidin-25 has been shown to be elevated in patients who do not develop acute kidney injury. Creatinine is an unreliable indicator during acute changes in kidney; therefore, the aim of the study was to assess whether hepcidin could predict renal outcome in 31 consecutive patients undergoing kidney allograft transplantation. Serum hepcidin was evaluated before and after 1, 3, 6, and 10 days after kidney transplantation, using commercially available kits. Serum creatinine was assessed at the same time. METHODS: We found a significant decrease in serum hepcidin, as early as after 1 day after kidney transplantation. Before transplantation, serum hepcidin was related to creatinine. In patients with delayed graft function, there was no decrease in serum hepcidin. RESULTS: Our findings may have important implications for the clinical treatment of patients undergoing kidney transplantation. The "window of opportunity" is narrow in delayed graft function to distinguish between acute rejection and calcineurin inhibitors nephrotoxicity, and time is limited to introduce proper treatment after initiating insult. CONCLUSIONS: Hepcidin must be investigated as a potential early marker for delayed graft function, especially in the upcoming setting of early dialysis treatment or anti-rejection therapy and might contribute to early patient risk stratification.

High-performance Liquid Chromatography Measured Metabolites of Endogenous Catecholamines and Their Relations to Chronic Kidney Disease and High Blood Pressure in Heart Transplant Recipients.

BACKGROUND: Patients after solid organ transplantation, especially heart and kidneys, are prone to be hypertensive. Recently chronic kidney disease and renalase metabolism of endogenous catecholamines are thought to make major contribution to the pathogenesis of hypertension. MATERIALS AND METHODS: We analyzed 75 heart recipients (80% male, 20% female), medium age 54.9 years (range, 25-75) at 0.5 to 22 years after heart transplantation (median, 10.74). Diagnosis of hypertension was made on the basis of ambulatory blood pressure monitoring. Complete blood count, urea, creatinine, estimated glomerular filtration rate (eGFR), renalase in serum, and levels of metanefrine, normetanefrine, and 3-metoxytyramine in 24-hour urine collection calculated with a high-performance liquid chromatography were recorded. RESULTS: Urine endogenous catecholamine metabolites were estimated according to creatinine clearance. Normetanefrine was correlated with age (r = 0.27; P < .05), urea (r = 0.64; P < .01), creatinine (r = 0.6; P < .01), eGFR (r = -0.51; P < .01), renalase (r = 0.5; P < .01), and diastolic blood pressure (r = 0.26; P < .05). Metanefrine was correlated with urea (r = 0.43; P < .01), creatinine (0.32; P < .01), eGFR (r = -0.4; P < .01), renalase (r = 0.34; P < .05), height (r = -0.26; P < .05), weight (r = -0.23; P < .05), and time after heart transplantation (r = 0.27; P < .05). 3-Metoxytyramine was correlated with urea (r = 0.43; P < .01), creatinine (r = 0.32; P < .01), and the eGFR (r = -0.24; P < .05). Creatinine was correlated with age (r = 0.36; P < .01), diastolic blood pressure (r = 0.26; P < .05), time after heart transplantation (r = 0.24; P < .05), and renalase (r = 0.69; P < .01). Systolic blood pressure was correlated with proteinuria (r = 0.26; P < .05). CONCLUSIONS: Chronic kidney disease and concomitant hypertension are the most prevalent comorbidities in the population of heart transplant recipients. Urine catecholamine metabolites were related to kidney function but not to blood pressure level in the studied population.

Endocan Concentration and Chronic Inflammatory Process Among Heart Transplant Recipients.

BACKGROUND: Endocan is a novel soluble dermatan sulfate proteoglycan derived from endothelium. It has the capacity of binding to different biologically active molecules associated with cellular signaling, adhesion, and regulating proliferation, differentiation, migration, and adhesion of different cell types in health and pathology. Its elevated level is connected with endothelial activation, neovascularization, and inflammation or carcinogenesis. METHODS: The level of serum endocan among 131 heart transplant recipients on 3-drug immunosuppression (calcineurin inhibitor, mycophenolate mofetil/mycophenolic acid, steroid) in correlation with other markers of endothelial damage was determined. In addition, 22 healthy volunteers were studied. In cross-sectional study, markers were measured with the use of commercially available assays of endothelial damage-endocan and von Willebrand factor (VWF)-inflammation-high-sensitivity C-reactive protein (hsCRP), interleukin (IL) 6-and kidney function-cystatin C. RESULTS: The endocan, VWF, IL-6, hsCRP, and cystatin C levels were significantly higher in heart transplant recipients compared with healthy volunteers. In our cohort, endocan level was correlated with renal function (estimated glomerular filtration rate: r = -0.21; P < .05), creatinine (r = 0.21; P < .05), erythrocyte count (r = -0.24; P < .01), hemoglobin (r = -0.33; P < .01), N-terminal pro-B-type natriuretic peptide (r = 0.25; P < .01), cholesterol (r = -0.22; P < .05), LDL (r = -0.21; P < .05), New York Heart Association functional class (r = 0.21; P < .05), hsCRP (r = 0.32; P < .01), IL-6 (r = 0.31; P < .01), and VWF (r = 0.27; P < .01). In multifactorial analysis, the predictors of endocan levels were cholesterol level, cystatin C, and IL-6, predicting 54% of variability. CONCLUSIONS: Endocan concentration among heart transplant recipients is potentially connected with endothelial damage caused by subclinical inflammation resulting from hyperlipidemia.

Kaposi Sarcoma in the Genital Area in a Kidney Transplant Patient: A Case Report and Literature Review.

BACKGROUND: Kaposi sarcoma (KS) is a cancer with an incidence in patients after transplantation (Tx) that is 500 times greater than that in the healthy population. The risk of KS increases significantly during therapy, especially when immunosuppressive therapy with cyclosporine A (CsA) is used. Most cases of KS develop during the first 2 years after transplantation. After a KS diagnosis, it is recommended to reduce the doses of immunosuppressive medications. Conversion of immunosuppressive treatment into mammalian target of rapamycin (m-TOR) inhibitors is strongly suggested. PATIENTS AND METHODS: We present the case of a 65-year-old man with end-stage renal disease (ESRD) of unknown etiology, who had kidney transplantation in 2008. Immunosuppressive protocol was based on CsA, mycophenolate mofetil (MMF) and prednisolone (PRE). In 2011, during the dermatological consultation, on the penis glans a purple stain of uneven surface was noted. Histology study revealed the presence of KS. The treatment was modified. The patient was converted from CsA to everolimus. Before converting, the creatinine concentration was 1.79 mg/dl and proteinuria less than 0.3 g/day. RESULTS: The change in the scheme of immunosuppresion from CsA to everolimus was performed to treat the Kaposi sarcoma. Gradually, within a year, the KS was cured. However, the graft function deteriorated, and the graft was lost in one-years' time. CONCLUSION: We present the first documented case of KS in the genital area of a kidney patient. The reduction in the strength of immunosuppression, and the introduction of an m-TOR inhibitor, may have contributed to the deterioration of kidney function, however it was substantial in the treatment of KS.

Absolute and Functional Iron Deficiency Is a Common Finding in Patients With Heart Failure and After Heart Transplantation.

BACKGROUND: Anemia is relatively common in patients with heart failure and heart transplant recipients. Both absolute and functional iron deficiency may contribute to the anemia in these populations. Functional iron deficiency (defined as ferritin greater than 200 ng/mL with TSAT (Transferrin saturation) less than 20%) is characterized by the presence of adequate iron stores as defined by conventional criteria, but with insufficient iron mobilization to adequately support. The aim of this study was to determine prevalence of absolute and functional iron deficiency in patients with heart failure (n = 269) and after heart transplantation (n = 130) and their relation to parameters of iron status and inflammation. METHODS: Iron status, complete blood count, and creatinine levels were assessed using standard laboratory methods. C-reactive protein, hepcidin and hemojuvelin were measured using commercially available kits. RESULTS: Absolute iron deficiency was present in 15% of patients with heart failure and 30% in heart transplant recipients, whereas functional iron deficiency was present in 18% of patients with heart failure and 17% in heart transplant recipients. Functional iron deficiency was associated with significantly higher C-reactive protein and hepcidin levels in heart failure patients, and higher hepcidin and lower estimate glomerular filtration rates in heart transplant recipients. Prevalence of anemia (according to the World Health Organization) was significantly higher in heart transplant recipients (40% vs 22%, P < .001), they were also younger, but with worse kidney function than patients with heart failure. CONCLUSIONS: Both absolute and functional iron deficiency were present in a considerable group of patients. This population should be carefully screened for possible reversible causes of inflammation.

Inadequate blood pressure control in orthotopic heart transplant: is there a role of kidney function and immunosuppressive regimen?

INTRODUCTION: Cardiac transplantation is the definitive therapy for eligible patients with end-stage heart failure. Hypertension is a widely accepted risk factor for its outcome. PATIENTS AND METHODS: We analyzed 169 heart transplant recipients. The diagnosis of hypertension was made on the basis of information gathered at 3 consecutive visits. Complete blood count, urea, serum lipids, fasting glucose, creatinine, and N-terminal pro-B-type natriuretic peptide were also studied. RESULTS: In the orthotopic heart transplantation (OHT) population, 11% had diabetes and 68% had chronic kidney disease. Hypertension was diagnosed and treated in 68% of the OHT patients. Hypertensive patients were significantly older, with a lower estimated glomerular filtration rate and higher serum creatinine and erythrocyte count. Thirty-three percent of patients did not achieve target blood pressure despite optimal medical treatment. Patients treated with tacrolimus had similar systolic blood pressure compared with those treated with cyclosporine (with a tendency to have lower values). Patients treated with mammalian target of rapamycin inhibitors had similar systolic and diastolic blood pressures compared with those treated without these inhibitors. In the group of patients given steroids, systolic and diastolic blood pressures were significantly lower than in the group not treated with steroids. In addition, steroid-treated patients had a significantly lower estimated glomerular filtration rate, hemoglobin, and erythrocyte count and higher serum creatinine, N-terminal pro-B-type natriuretic peptide, and New York Heart Association class. Chronic kidney disease was also more prevalent in this group. Blood pressure was not related to the kidney function. CONCLUSIONS: Despite polytherapy, optimal blood pressure control was not achieved in the majority of patients. OHT patients have a high prevalence of hypertension, which should be treated adequately. More efforts should be made to optimize blood pressure control, particularly when other comorbidities are present. Blood pressure was not related to patient kidney function.

Dopamine and noradrenaline are unrelated to renalase, heart rate, and blood pressure in heart transplant recipients.

INTRODUCTION: Renalase may degrade catecholamines and regulate sympathetic tone and blood pressure. The aim of this study was to assess dopamine, norepinephrine, and renalase in 80 heart transplant recipients and 22 healthy volunteers and their correlations with heart rate, blood pressure control, type of hypotensive therapy, and renal function. PATIENTS AND METHODS: Renalase, dopamine, and norepinephrine were studied by using commercially available assays. RESULTS: Renalase levels were higher in heart transplant recipients compared with healthy volunteers, and noradrenaline levels were lower in the studied cohort patients than in the healthy volunteers. Noradrenaline was correlated with white blood cell count (r = -0.21, P < .05), copeptin (r = 0.41, P < .01), and left ventricular diameter (r = -0.29, P < .05), whereas dopamine was correlated in univariate analysis with white blood cell count (r = -0.22, P < .05), posterior wall of left ventricular diameter (r = 0.58, P < .01), and left atrium diameter (r = -0.31, P < .05). Neither noradrenaline nor dopamine was correlated with heart rate, blood pressure, kidney function, or New York Heart Association class. Noradrenaline was significantly higher in patients with elevated diastolic blood pressure (>90 mm Hg) compared with those with normal diastolic blood pressure (P < .05). Renalase was related to kidney function but was unrelated to catecholamines. CONCLUSIONS: Elevated renalase levels in heart transplant patients were related to kidney function but not linked to the sympathetic nervous system activity in this study population. In heart transplant recipients, these findings might suggest that sympathetic denervation and the modulation of ß-receptors persist.

Fibroblast growth factor 23 and Klotho as cardiovascular risk factors in heart transplant recipients.

BACKGROUND: Fibroblast growth factor (FGF) 23 is one of the most recently discovered FGFs. This phosphaturic hormone produced in bones is a risk factor for cardiovascular diseases and thus mortality. Klotho is an essential coreceptor for FGF23 and at the same time it is known as a "longevity" hormone. There are no data considering FGF23 and Klotho roles in heart transplant (HT) recipients. The aim of this study was to assess Klotho and FGF23 serum concentration in heart transplant recipients depending on immunosuppressive therapy regimen and comorbidities. METHODS: Eighty-four stable heart transplant recipients were enrolled in the study; 22 healthy volunteers served as control subjects. FGF23 and Klotho protein concentration, markers of renal function, such as cystatin C and neutrophil gelatinase-associated lipocalin (NGAL), and heart failure markers, such as copeptine and N-termiinal pro-B-type natriuretic peptide (NT-proBNP), were evaluated. RESULTS: FGF23 concentration was significantly higher in the HT group whereas Klotho protein was significantly lower. FGF23 correlated with creatinine level (r = 0.72; P < .001), estimated glomerular filtration rate (eGFR; r = -0.32; P < .01), cystatin C (r = 0.36; P < .01), NGAL (r = 0.51; P < .001), hemoglobin (r = -0.39; P < .001), NT-proBNP (r = 0.51; P < .001), high-density lipoprotein (HDL; r = 0.27; P < .05), intraventricular septum thickness (r = 0.42; P < .01) and right ventricular systolic pressure (r = 0.34; P < .05). Klotho protein correlated only with age (r = -0.21; P < .05), creatinine (r = -0.21; P < .05), and eGFR (r = -0.31; P < .01). FGF23 concentration was significantly higher in patients with eGFR <60 mL/min whereas Klotho protein was significantly lower. FGF23 predictors were renal function (creatinine concentration; ß = 0.45; P = .0001), HDL (ß = 0.33; P = .003), intraventricular septum thickness (ß = 0.38; P = .0003), and right ventricular systolic pressure (ß = 0.34; P = .003), explaining 70% of FGF23 variability. CONCLUSIONS: FGF23/Klotho system disorders in HT recipients are related to cardiovascular system function and kidney failure and could cause increased risk of cardiovascular disease.

Growth differentiation factor 15 is related to anemia and iron metabolism in heart allograft recipients and patients with chronic heart failure.

BACKGROUND: Growth differentiation factor (GDF) 15 was recently identified as a hepcidin-suppression factor that is expressed at high levels in patients with ineffective erythropoiesis. Hepcidin is a small defensin-like peptide whose production by hepatocytes is modulated in response to anemia, hypoxia, or inflammation. The aim of this study was to assess GDF15 levels and its correlation with iron parameters in 134 stable heart transplant recipients compared with 157 patients with chronic heart failure (CHF). METHODS: Complete blood count, urea, creatinine, lipids, fasting glucose, and iron status were studied with the use of standard laboratory methods. We assessed GDF15, hepcidin, and soluble transferrin receptor (sTfR) with commercially available assays. RESULTS: Mean levels of GDF15 and hepcidin were significantly higher in heart allograft recipients compared with patients with chronic heart failure (P < .001). GDF15 was significantly higher in patients with anemia compared with nonanemic counterparts in both groups. In univariate analysis in heart transplant recipients, GDF15 was related to kidney function, age, time after transplantation, hepcidin, sTfR, hemoglobin, transferrin saturation, ejection fraction (EF), and New York Heart Association functional class. GDF15 was not related to serum iron or ferritin in both groups. In multivariate analysis, sTfR, creatinine, and age were found to be predictors of GDF15. In univariate analysis in CHF patients, GDF15 was related to creatinine, erythrocyte count, hemoglobin, hepcidin, and total iron binding capacity and tended to correlate with EF. In multivariate analysis, hepcidin, creatinine, and EF were found to be predictors of GDF15 in CHF. CONCLUSIONS: GDF15, by affecting iron status, might be involved in the pathogenesis of anemia in patients with cardiovascular pathology.

Zonulin and iron metabolism in heart transplant recipients.

BACKGROUND: In patients after heart transplantation, anemia is relatively common and is associated with impaired kidney function, subclinical inflammatory state, and immunosuppressive treatment. Zonulin-prehaptoglibin-2 is newly discovered protein with poorly defined function. Hemoglobin binds haptoglobin, and this stable complex prevents oxidative stress caused by hemoglobin. Zonulin is necessary for integrity of intracellular tight junction in the gut. Taking into consideration iron metabolism, including its absorption in the gut, the aim of this study was to assess zonulin levels in heart transplant recipients and their possible correlations with iron status, immunosuppressive therapy, and kidney function. METHODS: The study was performed with 80 stable heart transplant recipients and 22 healthy volunteers. Zonulin, iron status, and inflammatory markers were assessed with the use of commercially available kits. RESULTS: Zonulin correlated with intraventricular diameter (r = 0.30; P < .05), right ventricle systemic pressure (r = 0.27; P < .05), and hemoglobin (r = 0.21; P < .05). There were no correlations between zonulin and iron status. Zonulin was significantly lower in heart transplant recipients than in healthy volunteers (P < .001). Kidney function, immunosuppressive regimen, New York Heart Association functional class, sex, and presence of anemia did not affect zonulin level. CONCLUSIONS: Zonulin, despite its effect on the absorption of different nutrients and other substances and hypothethic role in oxidative stress, seems not to play a role in the pathogenesis of anemia in heart transplant recipients. Its physiologic role remains obscure.

YKL-40, a novel marker of cardiovascular complications, is related to kidney function in heart transplant recipients.

BACKGROUND: YKL-40 is an inflammatory glycoprotein involved in endothelial dysfunction and expressed in macrophages in the earliest lesions of atherosclerosis. Elevated serum YKL-40 levels are independently associated with the presence and extent of coronary artery disease and cardiovascular mortality. Because there are no data on heart transplant recipients and because they are prone to cardiovascular complications, the aim of this study was to assess YKL-40 in this population with particular attention to its relationship with endothelial damage. We studied 84 patients after heart transplantation. Healthy volunteers served as control subjects. METHODS: Complete blood count, urea, creatinine, lipids, fasting glucose, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and iron status were studied with the use of standard laboratory methods. We assessed YKL-40, copeptin, markers of inflammation high sensitivity C-reactive protein (hsCRP) and interleukin (IL) 6, and markers of endothelial cell injury von Willebrand factor (vWF) and midkine with the use of commercially available assays. RESULTS: Mean levels of YKL-40, IL-6, vWF, and hsCRP were significantly higher in heart allograft recipients than in the control group (P < .001). In univariate analysis, YKL-40 was related to kidney function (creatinine, r = 0.63 [P < .001]; estimated glomerular filtration rate, r = -0.44 [P < .001]), NT-proBNP (r = 0.45; P < .001), age (r = 0.33; P < .01), time after transplantation (r = 0.23; P < .05), copeptin (r = -0.42; P < .001), soluble transferrin receptor (r = 0.24; P < .05), hemoglobin (r = -0.42; P < .001), transferrin (r = -0.31; P < .01), haptoglobin (r = 0.39; P < .001), cystatin C (r = 0.55; P < .001), ejection fraction (r = -0.28; P < .05), New York Heart Association functional class (r = -0.41; P < .01), hsCRP (r = 0.26; P < .05), IL-6 (r = 0.23; P < .05), vWF (r = -0.40; P < .001), and midkine (r = 0.33; P < .01). In multivariate analysis, only creatinine was found to be a predictor of YKL-40 (ß = 0.59; P = .02), explaining 56% of the variation in YKL-40 levels in heart allograft recipients. CONCLUSIONS: YKL-40 may contribute to the enhanced risk of cardiovascular complications mainly owing to impaired renal function in patients after heart transplantation.