Gokhan Temiz

Acute Renal Failure under Dasatinib Therapy

Dasatinib is a second-generation tyrosine kinase inhibitor that is approved for the treatment of imatinib-resistant or imatinib-intolerant chronic myeloid leukemia. It has a 325 times stronger in vitro activity against to native BCR-ABL when comparing with imatinib. Little is known about the effects of dasatinib on renal function. A literature review revealed only one case with imatinib-resistant chronic myeloid leukemia that developed renal failure after being placed on dasatinib therapy. Here we report a patient with imatinib-resistant chronic myeloid leukemia who developed gastroenteritis and acute renal failure after a short time from the initiation of dasatinib therapy. After dasatinib interruption, these side effects resolved completely in days. In summary, dasatinib is a potent drug in the treatment of chronic myeloid leukemia, but close clinical monitoring and the timely interruption of the therapy in patients who developed acute renal failure are warranted.

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.

Renal hemosiderosis and rapidly progressive glomerulonephritis associated with primary hemochromatosis

Abstract Hereditary hemochromatosis leads to the accumulation of iron in many organs including the liver, spleen and heart and results in injury and dysfunction of these organs. On the other hand, iron accumulation and functional impairment in kidney is extremely rare. We report a 61-year-old male patient with hereditary hemochromatosis, in whom the renal function was deteriorated rapidly. Renal biopsy revealed crescentic glomeruli and hemosiderin accumulation in tubular epithelial cells.

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.

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.

Cerebral Sinovenous Thrombosis Associated with Factor V Leiden and Methylenetetrahydrofolate Reductase A1298C Mutation in Adult Membranous Glomerulonephritis

Abstract Thromboembolic diseases are accepted as the most important complications in adult nephrotic syndrome, particularly membranous nephropathy. As renal vein thrombosis is usually seen in patients with membranous nephropathy, cerebral venous thrombosis is a very rare condition, which has not been reported previously in adult patients with membranous nephropathy. Although acquired dysfunctions of coagulation and fibrinolytic systems are responsible for hypercoagulopathy in patients with nephrotic syndrome, the two most common causes of hereditary venous thrombosis [the mutations of factor V Leiden and methylenetetrahydrofolate reductase (MTHFR)] facilitate thrombosis in arterial and venous system in these patients. We report a 56-year-old man with sinovenous thrombosis, diagnosed as membranous nephropathy and detected to have mutations in factor V Leiden and MTHFR A1298C. Our patient is important because he had genetic risk of thrombotic conditions and was the first adult patient with membranous nephropathy.

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.

Late Effects of Renal Transplantation on Endothelial Functions and Cardiac Morphology

BACKGROUND Endothelial dysfunction is common in patients undergoing hemodialysis (HD), and cardiovascular morbidity and mortality are higher in these patients. In this study, we evaluated the late posttransplantation effects of cyclosporine and tacrolimus on endothelial function, inflammation, and cardiac architecture. METHODS The study included 12 patients undergoing hemodialysis (group 1); 22 renal transplant recipients, of which 13 were receiving cyclosporine therapy (group 2) and 9 were receiving tacrolimus therapy (group 3); and 12 healthy control individuals (group 4). Kidney recipients were included if the transplantation procedure had been performed at least 1 year before the study. Asymmetric dimethylarginine, C-reactive protein, carotid intima-media thickness, left ventricular posterior wall thickness, interventricular septal thickness, left ventricular muscle mass index, flow-mediated dilation, and nitroglycerine-induced dilation of the brachial artery were evaluated. RESULTS Serum asymmetric dimethylarginine, C-reactive protein, carotid intima-media thickness, left ventricular posterior wall thickness, interventricular septal thickness, and left ventricular muscle mass index values were significantly higher in patients undergoing HD than in the other 3 groups (P < .05), whereas percent change in flow-mediated dilation and nitroglycerine-induced dilation of the brachial artery was significantly lower (P < .05). CONCLUSION Patients undergoing HD demonstrate endothelial dysfunction. In the late posttransplantation period, kidney recipients seem to have similar endothelial function and cardiac architecture as in the healthy population. This result may explain the reduction in cardiovascular morbidity and mortality after transplantation in patients undergoing HD. Tacrolimus and cyclosporine have similar effects on endothelial function.

Assessment of genetic risk factors for thromboembolic complications in adults with idiopathic nephrotic syndrome.

AIMS Nephrotic syndrome (NS) may occur with acquired hypercoagulability, however, the fact that it is accompanied by an underlying hereditary thrombophilia, especially combined hereditary thrombophilia would lead to thrombotic events. In this study, we aimed to evaluate the contribution of genetic thrombophilia to development of thrombotic events in adult patients with NS. MATERIAL AND METHODS Factor V Leiden (FVL), prothrombin, and methylenetetrahydrofolate reductase (MTHFR) gene mutation were studied in 51 newly diagnosed idiopathic NS patients and age- and gender-matched 20 healthy control subjects included in the study. Renal vein Doppler ultrasound was conducted in order to investigate the prevalence of subclinical renal vein thrombosis. RESULTS Of 51 patients, 6 (11.8%) were established to have thromboembolic (TE) complications at the time of diagnosis (4 symptomatic, 2 subclinical), and no recurring thrombotic episode was observed. Genetic mutation was established in all patients that were found to have TE complications. Acquired hypercoagulability factors were similar in patients without and with TE complication. CONCLUSIONS The coexistence of inherited thrombophilia in NS may facilitate thromboembolic complications. If the cause of thrombosis cannot be explained by the usual factors attributed to the occurrence of thrombosis in NS, screening for the other factors, such as FVL, MTHFR, and prothrombin gene mutation, may be beneficial.

Rapid molecular cytogenetic diagnosis of transfusion associated graft-versus-host disease by fluorescent in situ hybridization (FISH)

Transfusion associated graft-versus-host disease (TA-GVHD) is a rare, dreadful complication of transfusion in immunocompromized and immunologically competent individuals. The diagnosis is often delayed, because of lack of awareness and the non-specific clinical features. We describe a rapid molecular cytogenetic analysis of FISH for the diagnosis of two cases of TA-GVHD with sex-mismatched donors. The use of FISH is a rapid and sensitive technique for the early diagnosis of TA-GVHD when the recipient and donor are of different gender.