Garip Sahin

Effect of N-Acetylcysteine on Endothelial Dysfunction in Dialysis Patients

Background/Aims: Patients with K/DOQI stage 5 chronic kidney disease (CKD) have higher incidence of cardiovascular events due to the oxidative stress and endothelial dysfunction (ED). The aim of this study is to evaluate the effects of N-acetylcysteine (NAC), which might prevent cardiovascular events by improving oxidative stress on endothelial cells in patients with CKD. Methods: Thirty uremic patients (age 40 ± 12 years, 6 males) on hemodialysis (HD) were evaluated for ED by using high-resolution Doppler ultrasound of brachial artery before and after 6 weeks of oral NAC (2 × 600 mg) medication. Also, 13 healthy controls (35 ± 9 years, 5 males) were included in the study. Reactive hyperemia following 5 min forearm ischemia was accepted as endothelium-dependent vasodilatation (flow-mediated dilatation; FMD) and compared to endothelium-independent vasodilatation in response to sublingual glyceril trinitrate (GTN). Results: Patients on HD had lower ΔFMD (0.28 ± 0.17 vs. 0.41 ± 0.11, p < 0.05) and FMD% (7.5 ± 5.05 vs. 11.33 ± 2.95, p < 0.05) than the controls. Baseline ΔGTN and GTN% were similar in two groups. NAC treatment significantly increased the ΔFMD (0.41 ± 0.11, p < 0.001 vs. baseline) and FMD% (10.59 ± 3.22, p < 0.01 vs. baseline) of patients on HD, while it had no effect on ΔGTN and GTN%. Conclusion: These results suggest that NAC treatment could improve the ED by preventing the reduction of FMD in patients on HD.

Effect of Sertraline Hydrochloride on Cardiac Autonomic Dysfunction in Patients with Hemodialysis-Induced Hypotension

Background/Aims: It was previously shown that sertraline hydrochloride treatment improved hemodynamic parameters of patients with dialysis induced hypotension (DIH). The aim of this study was to examine the effect of sertraline on the autonomic functions of patients with DIH. Methods: Ten patients with DIH, 10 hemodialysis patients without DIH and 10 healthy control subjects were included into the study. All of the patients were treated with sertraline 50 mg per day for 4 weeks. Pre-treatment and post-treatment heart rate variability (HRV) in supine and tilt position was evaluated. In order to evaluate the autonomic response to tilt position, gap values were calculated by subtracting the HRV in supine position from the HRV in tilt position. Results: Analysis of the HRV response to tilt, demonstrated a paradoxical reduction in the indices of sympathetic modulation and sympathovagal balance in the patients with DIH while there was an increase in normalized powers of low frequency components (LFNU) and low frequency to high frequency components ratio (LFP/HFP) in the patients without DIH and control group. The number of therapeutic interventions for restoration of DIH decreased significantly in the sertraline period (p < 0.001). The gap values of the patients with DIH in LFNU (sympathetic modulation) (p < 0.05) and LFP/HFP (sympathovagal balance) increased in the sertraline period (p < 0.01). The decrease in gap value of normalized powers of high frequency components (parasympathetic modulation) was pronounced in the sertraline period in the patients with DIH (p < 0.05). Conclusion: The preventive effect of sertraline on DIH might be related to the improvement of regulation of autonomic response to hypovolemia.

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.

Inappropriate use of nonsteroidal anti-inflammatory drugs and other drugs in chronic kidney disease patients without renal replacement therapy.

Abstract Objective: The main goal of chronic kidney disease (CKD) treatment is the prevention of progression of the disease and complications. Inappropriate drug use in patients with CKD is an important issue, which may cause adverse effects on patients and progression of chronic renal failure. The aim of this study is to find the rate of inappropriate drug use among CKD patients. Methods: The subjects of this study were selected from the patients with a CKD history of minimum one year, who did not receive renal replacement therapy. Patients were asked to provide a digital record of the drugs they used over the last one year. Individually, for each patient, the drugs that may be contraindicative and that require dose adjustment were identified based on glomerular filtration rate (GFR). Results: This study includes a total of 185 participants – 97 female (52.4%) and 88 male (47.6%) patients. The average age of patients was 60.50 ± 14.56. It was shown that 149 patients (80.5%) were using inappropriate drugs. Seventy (47.0%) were using one, 79 (53.0%) two, 30 (20/1%) three, and 9 (6.4%) four inappropriate drugs. Of CKD patients, 44.3% were aged 65 or over; and in this age group, inappropriate drug use was more frequent compared to the population below 65 (86.6% vs. 75.7%). The drugs used inappropriately were, respectively, nonsteroidal anti-inflammatory drugs (65.8%), quinolone antibiotics (39.0%), ACE inhibitors (26.9%). Discussion: Health professionals are required to consider renal functions of all patients, mainly those aged over 65, when administering a treatment.

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.

An Unusual Presentation for Nephrotic Syndrome

We present a 30-year-old man with nephrotic syndrome presenting with bilateral perirenal massive collection compatible with transudation. After drainage of collections kidney biopsy was performed and the histologic diagnosis was focal and segmental glomerulosclerosis. The patient was treated with cyclophosphamide, prednisone, furosemide and enalapril. After remission of nephrotic syndrome renal ultrasound showed complete resolution of perirenal collections. In conclusion, the case shows that perirenal subcapsular transudation is a rare complication of nephrotic syndrome and massive collections can be treated successfully by percutaneous drainage.

Acute and subacute effects of EV iron sucrose on endothelial functions in hemodialysis patients.

Background: Iron support is an important component of treatment of anemia in hemodialysis (HD) patients. However, there are concerns about endovenous (EV) iron therapy that may cause endothelial dysfunction (ED) by increasing oxidative stress (OS) and lead to cardiovascular events. In this study, we aimed to evaluate the effects of high and repeated doses of EV iron sucrose on endothelial functions in acute and subacute phases. Methods: We included 15 HD patients to our study. There were 16 patients with iron deficiency but normal kidney functions in control group. We also evaluated endothelium-dependent vasodilatation (EDV) and nitroglycerin-induced vasodilatation (NIV) from the brachial artery by ultrasonography at the beginning of the study, and then 200 mg EV iron sucrose was given initially to both groups for 1 h in 250 cc 0.9% saline and 4 h after the end of the infusion (acute phase) sonographic vasodilatation parameters were measured from brachial artery. These measurements and laboratory tests were repeated 1 week after the end of a total 1000 mg EV iron sucrose replacement (200 mg/week). Results: There was a statistically significant increase in hemoglobin and ferritin levels after the EV iron sucrose therapy in both control and patient groups. EDV values in the HD group were significantly lower than that in the control group before therapy (6.25% vs. 10.53%, p < 0.05). EV iron sucrose therapy did not alter EDV and NIV values at the 4th hour and 6th week in both control and patient groups. Conclusion: According to our study, compared with the control group with normal kidney functions, HD patients had impaired endothelial functions. However, in HD patients, high and repeated doses of EV iron sucrose do not have deleterious effects on endothelial functions at acute and subacute phases and can be used safely in that patient group.