Impact of immunosuppressive treatment on the cardiovascular system in patients after hand transplantation.

BACKGROUND: Cardiovascular disease is a major cause of mortality in solid organ allograft recipients. Hand transplantation is not a lifesaving procedure, thus the effect of long-term immunosuppression on the cardiovascular system in these patients should be monitored. The aim of this study was to evaluate the morphology and function of heart and blood vessels in patients after hand transplantation. METHODS: The study included 5 patients at ages 32 to 58 years, mean 39 years, who underwent hand transplantation between 2006 and 2010. Immunosuppressive treatment included basiliximab in induction and tacrolimus, mycophenolate mofetil, and prednisone. Cardiac status was assessed by echocardiography (according to the American Society of Echocardiography) and cardiac biomarkers. Blood vessels were estimated by carotid intima-media thickness, pulse wave velocity, and brachial artery flow-mediated dilatation (FMD). The examinations were performed at 28 to 79 (mean 43) months after transplantation. RESULTS: Cardiovascular risk factors were observed in all patients after transplantation: 2 had insulin-dependent diabetes, 3 developed dyslipidemia and hypertension, 2 had chronic kidney disease stage 3. Concentric left ventricular hypertrophy was found in 1 and ventricular concentric remodeling in 4 patients. Impaired diastolic function (E/e' > 8) was observed in 2 patients. The index volume of the left atrium was higher in all patients. The cardiac biomarkers N-terminal pro-brain natriuretic peptide, C-reactive protein, and troponins were within normal range. Carotid intima-media thickness was higher in 1 patient and normal in 4 patients. Arterial stiffness measured by pulse wave velocity was not increased in all patients. Native brachial artery FMD response, an index of endothelium-dependent function, was abnormal in 2 patients, but in the transplanted extremity FMD was abnormal in 4 patients. CONCLUSIONS: Pathologic changes in cardiac structures were found in all patients, but the arterial wall changes and endothelial dysfunction were observed in some patients. Patients after hand transplantation are at higher risk for cardiovascular disease.

Effect of reduced sympathetic hyperactivity on cardiovascular risk factors in kidney transplantation patients.

BACKGROUND: Hyperactivity of the sympathetic nervous system caused by chronic kidney disease has detrimental effects on hypertension and cardiovascular morbidity. Kidney transplantation does not ameliorate sympathetic nerve overactivity; however, bilateral nephrectomy eliminates it. The aim of the study was to evaluate the effect of bilateral nephrectomy on risk factors for cardiovascular morbidity and mortality in long-term follow-up. MATERIAL AND METHODS: We studied 24 kidney recipients aged 44 ± 13 years who had undergone native bilateral nephrectomy. The control group included 17 recipients with preserved native kidneys who were matched for age, gender, cause of end-stage renal disease, immunosuppressive treatment, and time after transplantation. The mean follow-up after transplantation was 103 months. We evaluated arterial blood pressure, pulse pressure, metabolic markers, allograft function, echocardiography, and cardiac morbidity in all patients throughout follow-up. RESULTS: Systolic and diastolic blood pressures, number of antihypertensive drugs, and pulse pressure (a marker of arterial stiffness), were significantly lower among the study versus the control group (P < .05). The left ventricular mass, left ventricular mass index, left ventricular posterior wall thickness, and interventricular septum thickness were also lower in the study than in the control group (P < .05). Cardiac morbidity, including ischemic heart disease, atrial fibrillation, heart failure and stroke, occurred in 4 (16%) study group and 6 (35%) control subjects. Metabolic disorders, namely, new onset diabetes after transplantation, hyperuricemia, and dyslipidemia, occurred with similar frequencies in both groups. Serum levels of creatinine and estimated glomerular filtration rates were comparable in both groups, remaining stable throughout the observation time. CONCLUSIONS: Reduction of sympathetic hyperactivity by nephrectomy improved blood pressure control as well as decreased arterial stiffness and left ventricular hypertrophy over long-term follow-up. These results support native renal denervation to prevent the harmful effects of sympathetic hyperactivity on the cardiovascular system of renal transplant recipients.

[Homocysteine as a nonlipid factor in the pathogenesis of atherosclerosis]. / Homocysteina nielipidowym czynnikiem patogenezy miazdzycy.

Genetic abnormalities in two metabolic steps in homocysteine degradation: transsulfuration and remetylation can cause raised plasma homocysteine concentration. Homocysteine appeared to be an independent arteriosclerotic risk factor in the coronary, cerebral and peripheral circulation and elevated homocysteine levels have been found in chronic renal failure patients undergoing hemodialysis treatment and in transplant patients as well. Homocysteine has a direct toxic effect on endothelial cells, reduces normal activation of protein C by endothelial cells, increases the binding of Lp(a) to plasmin-modified fibrin, induces tissue factor procoagulant activity and inhibits the cofactor activity of thrombomodulin. Treatment with folic acid and piridoxine can lower the high level of homocysteine and should be associated with a clinical benefit.

[The effect of long term erythropoietin treatment on levels of free amino acids in patients with long term hemodialysis]. / Wplyw dlugotrwalego leczenia erytropoetyna na poziom wolnych aminokwasów u chorych przewlekle hemodializowanych.

In order to assess the effect of erythropoietin (Epo) treatment on amino acids profile in hemodialysis patients (HD pts) 2 groups of pts were analyzed: I-12 pts HD for 146 +/- 71 months, Epo treated for 64 +/- 10 months, II-17 pts HD for 120 +/- 39 months, non Epo treated, mean Hb 11.5 +/- 1.2 g/dl. Controls consisted of 11 healthy individuals. Amino acids were estimated by HPLC OPA method. In group I blood levels of leucine (p < 0.03), valine (p < 0.002) were decreased and alanine (p < 0.05) was increased when compared to controls. In this group, blood levels of methionine, tyrosine and asparagine were elevated (p < 0.04) when compared to group II but they were lower (about 30%) then in controls. In group II pts showed reduced levels of valine (p < 0.008), leucine (p < 0.001), methionine (p < 0.0001), tyrosine (p < 0.003), asparagine (p < 0.04), whereas serine, glutamate and alanine (p < 0.04) were increased when compared to controls. Essential to nonessential amino acids ratios in group I, II and controls were as follows: 0.17; 0.12; 0.49 respectively. There were not substantial differences in amino acids in pts with elevated or normal PTH level in both HD groups. Long term EPO treatment only partially corrected changes in amino acids levels in pts with chronic renal failure.

[Treatment with human recombinant erythropoietin and nutritional status of patients on lon term dialysis]. / Leczenie ludzka rekombinowana erytropoetyna a stan odzywienia chorych dlugotrwale dializowanych.

UNLABELLED: In order to assess the effect of long term erythropoietin (EPO) therapy on the nutritional status of hemodialysed (HD) patients 2 groups of HD patients were studied: I-EPO treated for 72 +/- 8 mo, 12 patients, HD for 138 +/- 66 mo, II-control group, 14 patients with Ht 30%, HD for 121 +/- 35 mo. At the onset and after 6 years of follow up patients underwent the following examination: length, body weight, body mass index, body fat stores, arm muscle circumference and total serum protein, serum albumin, lymphocyte count, creatinine, urea, cholesterol and PTH. In EPO group mean BMI, body fat, arm muscle circumference, visceral protein and total lymphocyte count were not change. In control group the decrease in height, body weight, BMI, body fat stores, arm muscle circumference and albumin were observed. Elevation of PTH estimated in half of patients in EPO group and 75% of patients in control group could influence the nutritional status of hemodialysed patients. CONCLUSION: 1. Nutritional status of majority of hemodialysed patients was not change during six years EPO therapy. 2. Non EPO treated patients showed the decrease of anthropometric measurements and serum albumin.

[Chlamydia trachomatis infection of the urogenital system in our clinical experience]. / Zakazenie Chlamydia trachomatis ukladu moczoplciowego we wlasnej obserwacji klinicznej.

The increased number of the genitourinary system infection caused by Chlamydia trachomatis (Ch. Tr.), increased number of patients with dysuria or sterile leukocyturia gave stimulus to studies of 615 patients from Department of Nephrology and District Outpatient Nephrological Care Unit with regard to infections with that microbes. Material for investigations derived from urethra. Diagnostic examinations were performed using the Mc Coy cell culture and the immunofluorescence method. The infection was noted in 176 patients (119 women and 57 men) that is in 28.6% of cases studied. The mean age of patients was 42.7 +/- 12 years. Clinical symptoms such as dysuria or frequency were typical for that kind of infection. The most frequent abnormality was leukocyturia or leukocyturia accompanied by erythrocyturia noted in 66% of patients. Isolated erythrocyturia was observed in 24.4% of cases. It has been stated that anamnesis or routine laboratory examinations were not able to the identification of infection. In face of poorly characteristics of clinical picture of infection the infection with Ch.Tr. could be the cause of unsuccessful therapy in patients with signs of genitourinary tract infections.

Effect of parathyroid hormone on energy metabolism of skeletal muscle.

Clinical states with primary or secondary hyperparathyroidism are associated with muscle dysfunction, suggesting that parathyroid hormone (PTH) may affect muscle metabolism. The present study examined the effect of 1-84 PTH and its amino-terminal fragment (1-34 PTH) on energy production, transfer, and utilization by skeletal muscle. Rats weighing 150 to 200 g were injected intraperitoneally with 1-84 or 1-34 PTH, 200 U/day, for 4 days, and control animals received vehicle only. The effect of the simultaneous administration of a calcium channel blocker, verapamil, was examined also. The muscle content of inorganic phosphorus, creatine phosphate, and adenine nucleotides were significantly (P less than 0.01) lower in the PTH-treated rats than in control animals. The hormone significantly reduced mitochondrial oxygen consumption without altering ADP:0 ratio, indicating reduced phosphorylation. Both 1-84 and 1-34 PTH produced significant (P less than 0.01) reduction in the activities of mitochondrial and myofibrillar CPK, and mitochondrial MgATPase. 1-84 PTH reduced the activity of myofibrillar CaATPase as well. There was a significant (P less than 0.01) increment in muscle uptake of 45Ca in the 1-84 PTH-treated rats. Verapamil abolished all the effects of PTH. Our data demonstrate that both 1-84 and 1-34 PTH impair energy production, transfer, and utilization. These biochemical derangements may, at least in part, underlie the myopathy observed in conditions associated with excess PTH.

Effect of parathyroid hormone on myocardial energy metabolism in the rat.

This study examined the effect of parathyroid hormone (PTH) on myocardial energy production, transfer, and utilization. Rats (150 to 200 g) were injected with 1-84 PTH, 200 U/day i.p., or 1-34 PTH, 200 or 300 U/day i.p., for 4 days. Control animals received the vehicle only. The effect of the simultaneous administration of calcium channel blocker, verapamil, was also examined. Myocardial contents of Pi, ATP, and CP were significantly (P less than 0.01) lower in the 1-84 PTH-treated rats than in control animals. Both 1-84 PTH and 1-34 significantly (P less than 0.01) reduced mitochondrial oxygen consumption without altering ADP:O ratio indicating reduced phosphorylation. 1-84 and 1-34 PTH significantly (P less than 0.01) reduced the activities of mitochondrial and myofibrillar creatine phosphokinase and 1-84 PTH inhibited (P less than 0.01) the activities of mitochondrial Mg ATPase and those of myofibrillar Ca ATPase. There were significant (P less than 0.01) increments in myocardial 45Ca and in total calcium content in 1-84 PTH-treated rats. Verapamil abolished all the effects of 1-84 PTH. Similarly, inactivation of 1-84 PTH abolished its effects. Treatment with 1-84 PTH for 10 days was associated with a significant decrease in cardiac index and mean arterial pressure. Our data demonstrate that both 1-84 and 1-34 PTH impair energy production, transfer, and utilization. These biochemical derangements, if maintained, produce a decrease in cardiac index. It appears that the enhanced entry and the accumulation of calcium in the myocardium, either directly and/or indirectly, are responsible for the action of PTH on energy metabolism of the heart.