Ahmet Ugur Yalcin

Effect of spironolactone on impaired fibrinolysis of hypertensive patients.

Background/Aims: Angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists have beneficial effects on impaired fibrinolytic activity of hypertensive patients. The aim of the study was to evaluate the effect of antialdosterone treatment on impaired fibrinolysis of hypertensive patients. Methods: Fourteen hypertensive outpatients and 14 normotensive healthy volunteers participated in this study. Blood samples for plasminogen activator inhibitor-1 (PAI-1) antigen and tissue plasminogen activator (t-PA) antigen were obtained at baseline in all patients and control subjects. Then all hypertensive patients used spironolactone 50 mg/day for a week. Blood samples were again obtained after a week of spironolactone treatment. Results: The mean basal plasma level of PAI-1 of hypertensive patients was higher than those of the normotensive control group (60.98 ± 4.2 vs. 24.09 ± 1.61 ng/ml, p < 0.01) The mean basal t-PA level was similar in the hypertensive and control subjects (7.49 ± 0.65 vs. 8.78 ± 0.92 ng/ml, p > 0.05). The mean PAI-1 level decreased after a week of spironolactone treatment (60.98 ± 4.2 vs. 42.99 ± 7.98 ng/ml, p < 0.05). The mean plasma t-PA level of hypertensive patients increased after spironolactone treatment (7.49 ± 0.65 vs. 11.09 ± 1.33 ng/ml, p < 0.05). Conclusion: This study shows that spironolactone improves impaired fibrinolysis in systemic hypertension. It provides evidence for a direct link between aldosterone and the fibrinolytic system in humans.

The Effect of Low-Dose Cholecalciferol and Calcium Treatment on Posttransplant Bone Loss in Renal Transplant Patients : A Prospective Study

Background/Aim. Posttransplant steroid doses have been reduced with the use of new and potent immunosuppressive agents. However, posttransplant osteoporosis is still a serious problem. Our aim in this study was to investigate the effect of low-dose cholecalciferol and calcium supplementation on bone loss after transplantation in renal transplant patients. Methods. Fifty-eight renal transplantation patients were included in the study. Fourteen newly transplanted patients (group 1) and 44 renal transplantation patients with a graft age of at least six months (group 2) were involved. All patients received 400 IU/day orally cholecalciferol (vitamin D3) and 600 mg/day orally calcium replacement starting from the second day posttransplantion. All patients baseline serum and urine biochemistry, serum 25-hydroxy vitamin D3 (25 (OH)D3), and bone mineral density (BMD) tests were performed. Also, the same measurements were performed at the 12th month in group 1. Results. After one year of treatment, BMDs were improved in group 1. Patients in group 1 had a nonsignificant increase of lumbar spine (8.12 ± 18.64% of baseline BMD) and femoral total (7.10 ± 13.48% of baseline BMD) BMD at the end of the first year. On the other hand, there was a significant increase in femoral neck (10.06 ± 15.70% of baseline BMD, p < 0.05) measurements. The baseline results of group 2 were similar to group 1. In group 1, 25 (OH)D3 levels were increased while PTH levels were decreased at the end of the year. Conclusion. In renal transplant patients who use low-dose metilprednisolon and new immunosuppressive agents together, low doses of vitamin D3 and calcium replacement for one year provides a reduction in lumbar spine, femoral neck, and femoral total bone loss and prevents bone loss in group 2. In addition, it contributed to the normalization of PTH levels.

Sertraline hydrochloride treatment for patients with hemodialysis hypotension.

Background: Recently some pathogenetic parallels have been drawn between dialysis-induced hypotension and disorders characterized by hemodynamic instability due to autonomic dysfunction, such as neurocardiogenic syncope and idiopathic orthostatic hypotension. Several studies have shown that central serotonergic pathways participate in the abnormal response, and selective serotonin reuptake inhibitors improve the symptoms of patients with neurocardiogenic syncope or idiopathic orthostatic hypotension. In order to evaluate the effectiveness of sertraline on dialysis-induced hypotension a prospective study was designed. Methods: The data of 9 patients from a 4-week pre-sertraline period were compared with the data of a 4-week sertraline (100 mg daily) period. The therapeutic effect of sertraline requires 4 weeks. Therefore the sertraline period was begun 4 weeks after starting the drug. Results: Post-hemodialysis weights and ultrafiltration volumes were similar in the pre-sertraline and sertraline periods. There were also no changes in hematocrit and serum albumin. Both systolic and diastolic blood pressure before dialysis remained unchanged during sertraline treatment. The nadir systolic blood pressure and systolic blood pressure after dialysis increased significantly in the sertraline period. The nadir diastolic pressure was also increased significantly but the increase in post-dialysis diastolic blood pressure did not reach statistical significance. The necessity of therapeutic interventions per dialysis session decreased significantly in the sertraline period compared with pre-sertraline period. Conclusions: This pilot study has shown that sertraline has the potential to be a safe and effective therapy for dialysis hypotension. Long-term clinical and pathophysiological studies are currently in progress.

Effects of immunosuppressive drugs on platelet aggregation and soluble P-selectin levels in renal transplant patients.

Background/aim. Post-transplant cardiovascular events are associated with increased morbidity and mortality after renal transplantation. Though renal transplantation eliminates cardiovascular disease risk factors by restoring renal function, it introduces new cardiovascular risks derived partly from immunosuppressive medications. In this study, to assess the effects of various immunosuppressive drugs on platelet function of renal transplant patients, we measured soluble P selectin levels (sP-selectin) and performed platelet aggregation studies in patients who have undergone renal transplantation. Methods. sP-selectin levels and platelet aggregation induced by 5 μM adenosine diphosphate (ADP), 5 μM epinephrine, 1.25 mg/mL ristocetin, and 2 μg/mL collagen were studied by whole blood platelet lumi-aggregometer in 40 renal transplant patients. Patients in group 1 (n = 24) were treated with cyclosporine/mycophenolate mofetil/methylprednisolone, and group 2 (n = 16) were treated with tacrolimus/mycophenolate mofetil/methylprednisolone. Effects were compared with those in control groups of hypertensive subjects and healthy subjects. Results. Platelet aggregation values induced by ADP, epinephrine, ristocetin, and collagen were lower in cyclosporine-treated patients than tacrolimus-treated patients, hypertensive subjects, and healthy subjects, though the difference was not statistically significant (p > 0.05). sP-selectin levels were appreciably higher in cyclosporine-treated patients, and statistically significant differences were observed compared with those of tacrolimus-treated patients (p < 0.05), hypertensive subjects (p < 0.01), and healthy subjects (p < 0.05). Conclusion. We conclude that cyclosporine-treated renal transplant patients show enhanced platelet activation in which anti-platelet therapy should be considered, in addition to management of other conventional cardiovascular risk factors, to decrease the cardiovascular morbidity and mortality in this high risk population.

Immune response after a single vaccination against 2009 influenza A H1N1 in hemodialysis patients

Background: Influenza infection is a significant cause of morbidity and mortality in general population. Hemodialysis patients are considered at high risk of influenza infection given their altered immune status. Pandemic influenza virus is new for human beings, so it is hard to predict the response to infection or vaccination. We aimed to evaluate the response to pandemic H1N1 vaccination in hemodialysis patients. Methods: A total of 70 patients on chronic hemodialysis and 20 controls who had been vaccinated against the pandemic influenza virus 5 weeks before the time of blood sampling were included into this study. The anti-H1N1 immunoglobulin G (IgG) antibodies of the patients were studied with enzyme immune assay (EIA) method. Our cut-off optical density (OD) value was 1.503. If the patients OD value was equal or higher than this value, it was considered as positive. If it was lower, it was considered as negative. Results: The mean OD value was 2.22 ± 0.42 in the patient group and 1.99 ± 0.34 in the control group (p < 0.05). Two of 70 patients and 1 of the controls had negative OD values and they were considered as nonresponsive to vaccination. There was also a negative correlation between the age and OD values in the patient group (r = −0.277, p < 0.05). Conclusion: H1N1 vaccine can be performed safely and cost effectively with a single dose to the risk groups especially to the hemodialysis patients. Evaluation of H1N1 IgG antibody with enzyme-linked immunosorbent assay (ELISA) may be a safe, easy, and cost-effective assay.

Recombinant factor VIIa treatment for life‐threatening haemoptysis

Abstract:  Diffuse alveolar haemorrhage is a severe clinical disorder that may be life‐threatening. The early diagnosis of diffuse alveolar haemorrhage and prompt intervention is crucial. Recombinant factor VIIa has been used extensively for the treatment of haemophilia A and B patients. More recently, recombinant factor VIIa has been used successfully for the treatment of bleeding in patients without pre‐existing coagulopathy. We describe the successful use of recombinant factor VIIa in a patient with diffuse alveolar haemorrhage secondary to pulmonary–renal syndrome.

Which statin should be used together with colchicine? Clinical experience in three patients with nephrotic syndrome due to AA type amyloidosis.

Colchicine and statins are well known drugs that cause myopathy and neuropathy. Co-administration of certain drugs with statins may increase myotoxic effect, causing myopathy and varying degrees of rhabdomyolysis. Therefore, it is very crucial to know which statin should be used during a combination therapy including colchicine and other drugs. We present three cases with AA amyloidosis secondary to familial Mediterranean fever, who developed neuromyopathy while receiving the combination of colchicine and statin. We also briefly discussed the different metabolic pathways of statins and colchicine when used together.

Effects of Lipoprotein-Associated Phospholipase A2 on Arginase/Nitric Oxide Pathway in Hemodialysis Patients

Lipoprotein-associated phospholipase A2 (Lp-PLA2) and arginase are recently described inflammatory biomarkers associated with cardiovascular disease. In this study, we aimed to investigate the possible effects of serum Lp-PLA2 mass levels on arginase/nitric oxide (NO) pathway as a cardiovascular risk marker in hemodialysis (HD) patients. Forty-three HD patients and 15 healthy subjects were included in this study. Lipid profile, high sensitivity C-reactive protein (hs-CRP), albumin, creatinine, body mass index (BMI), Lp-PLA2 and total nitrite levels, and arginase activity were determined in serum samples from patients and control subjects. Lp-PLA2 levels were found to be positively correlated with arginase, triglycerides, total cholesterol, low-density lipoprotein-cholesterol, and age and negatively correlated with high-density lipoprotein-cholesterol and total nitrite levels, while there was no correlation with BMI and hs-CRP, albumin, and creatinine levels in HD patients. We conclude that elevated Lp-PLA2 mass levels may contribute to impaired arginase/NO pathway in HD patients and that increased the arginase activity and Lp-PLA2 mass levels with decreased total nitrite levels seem to be useful biochemical markers in terms of reflecting endothelial dysfunction and associated cardiovascular risks in HD patients.

Effects of cinacalcet treatment on QT interval in hemodialysis patients

Objective: Cinacalcet is a calcimimetic drug that acts via calcium-sensing receptors (CaSRs) and increases the sensitivity of CaSRs on the parathyroid gland; thus, it lowers calcium and phosphorus levels as well as parathormone levels. Prolongation of the QT interval is recognized as a risk factor for the development of ventricular arrhythmias and sudden death. Patients with end-stage renal disease (ESRD) are sensitive for QT prolongation and torsade de pointes more than the normal population. In this study, we aimed to evaluate the effects of cinacalcet on the electrocardiogram (ECG), particularly changes in the QT interval, in patients with ESRD. Methods: Thirty-seven patients (21 males and 16 females) undergoing maintenance hemodialysis for at least 12 months were included in this retrospective study. Patients receiving cardioactive and antiarrhythmic drugs and those having a history of any cardiac or cerebrovascular events, active malignancy, and infections were excluded. Baseline ECG measurements of patients were performed over the newest ECG measurements that were obtained within 1 month before initiating the cinacalcet treatment, and the ECG measurements of patients after the cinacalcet treatment were performed according to the most recent ECG that was taken within the last 1 week in the clinic. We recorded the heart rate and QT values of patients before and after treatment and then calculated the corrected QT values (QTc). The Statistical Package for the Social Sciences (SPSS) ver. 21.0 was used for statistical analysis. Results: The mean age of patients was 52.24±14.49 years. Prolongation of QTc was statistically significant compared with the baseline QTc value (baseline: 396.62±42.04 msec; after treatment: 404.97±43.47 msec; p=0.031). We found a positive correlation between the prolongation of QTc and treatment dose of cinacalcet (p<0.005, r=0.560). Conclusion: Clinicians should be very careful for life-threatening cardiac side effects while increasing the dose of cinacalcet treatment in hemodialysis patients who have a borderline or prolonged QTc interval.

Autoimmune hypothyroidism and lupus-like syndrome

The frequency of thyroid disorders, particularly Hashimoto’s thyroiditis, may be increased in patients with connective tissue diseases. Both hypothyroidism and connective tissue diseases often cause muscle and joint aches, pains and stiffness. Skin, renal and cardiovascular involvement seen in the course of autoimmune hypothyroidism (AIH) may simulate connective tissue diseases such as systemic lupus erythematosus (SLE). We herein report a case of AIH who presented with massive proteinuria, haematuria, pleural fluid and arthritis simulating SLE.