Ismail Kirbas

A Randomized Study of Allopurinol on Endothelial Function and Estimated Glomular Filtration Rate in Asymptomatic Hyperuricemic Subjects with Normal Renal Function

BACKGROUND AND OBJECTIVES Endothelial dysfunction is an early manifestation of vascular injury and contributes to the development of atherosclerotic cardiovascular disease. Recent studies have implicated hyperuricemia as a risk factor for cardiovascular disease. We hypothesized that lowering uric acid in subjects with asymptomatic hyperuricemia with allopurinol might improve endothelial dysfunction, BP, estimated GFR (eGFR), and inflammatory markers. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Subjects with asymptomatic hyperuricemia and no history of gout and 30 normouricemic control subjects were enrolled in this 4-month randomized prospective study. Thirty hyperuricemic patients received 300 mg/d allopurinol and were compared with 37 hyperuricemic patients and 30 normouricemic subjects in matched control groups. Flow-mediated dilation (FMD), eGFR, ambulatory BP monitoring, spot urine protein-creatine ratio, and highly sensitive C-reactive protein were measured at baseline and at 4 months. RESULTS Age, gender, lipid profile, eGFR, hemoglobin, glucose, and level of proteinuria were similar in hyperuricemic subjects and controls at baseline. As expected, hyperuricemic patients had higher levels of highly sensitive C-reactive protein and lower FMD compared with normouricemic patients. Allopurinol treatment resulted in a decrease in serum uric acid, a decrease in systolic BP, an increase in FMD, and an increase in eGFR compared with baseline. No significant difference was observed in the control hyperuricemic and normouricemic groups. In a multiple regression analysis, FMD levels were independently related to uric acid both before (beta = -0.55) and after (beta = -0.40) treatment. CONCLUSIONS Treatment of hyperuricemia with allopurinol improves endothelial dysfunction and eGFR in subjects with asymptomatic hyperuricemia.

Influence of Obstructive Sleep Apnea on Fatty Liver Disease: Role of Chronic Intermittent Hypoxia

BACKGROUND: Currently the common pathogenetic mechanisms in nonalcoholic fatty liver disease (NAFLD) and obstructive sleep apnea (OSA) are gaining increased attention. The aim of this study is to find out the influence of chronic intermittent hypoxemia and OSA related parameters to the severity of NAFLD. METHODS: We examined the liver functions tests and ultrasonographic data of liver as well as markers of OSA severity (apnea-hypopnea index [AHI], oxygen desaturation index, minimum oxygen saturation, percentage of time spent with SpO2 < 90%) of 106 subjects. RESULTS: Fatty liver disease was diagnosed in 71 subjects (group 1), and the remaining 35 subjects were taken as controls (group 2). The prevalence of OSA was 71.2% versus 35.7% for group 1 and 2, respectively (P < .001). As NAFLD severity increased from mild to severe form, mean AHI and oxygen desaturation index values also increased significantly. Our multivariate analysis showed that AHI, oxygen desaturation index, lowest desaturation values, and percentage of sleep duration with SpO2 < 90% were independent predictors of NAFLD after adjustment for BMI, weight, and insulin resistance. Furthermore, the most correlated parameter for the severity of NAFLD was found as the duration of hypoxia during sleep. CONCLUSIONS: The prevalence of NAFLD was higher in patients with severe OSA, suggesting a role for nocturnal hypoxemia in the pathogenesis of fatty liver disease.

Nebivolol improves renal function in patients who underwent angioplasty due to renal artery stenosis: a pilot study.

Renal artery stenosis (RAS) is a progressive disease and may lead to chronic kidney disease by deterioration of renal functions. Endothelial dysfunction is an important causative factor for kidney damage after RAS revascularization. Nebivolol, a new generation beta blocker induces endothelium-related arterial relaxation by nitric oxide (NO) and may improve endothelial dysfunction. This pilot study tested the effect of nebivolol on the glomerular filtration rate (GFR) in a series of 33 patients with severe RAS (>70%) who underwent revascularization. After revascularization, nebivolol was added to antihypertensive treatment in 17 randomly selected patients while 16 patients (control group) continued their standard treatment. Estimated glomerular filtration rate (eGFR), proteinuria as well as nitrite and nitrate levels were measured at baseline and 6 months after the revascularization procedure. Six months after revascularization, eGFR increased from 44.8 to 50.6 ml/min in the nebivolol group. In contrast, eGFR did not change in the control group. Nitrite/nitrate levels decreased to a significant extent both in the nebivolol and in the control group. Proteinuria decreased more in the nebivolol group compared to the control group. These pilot data support a full-fledged clinical trial, testing whether nebivolol may be beneficial in the post-revascularization phase in patients with RAS.

Ultrasound and Computed Tomography Findings of Spontaneous Intramural Hemorrhage of Renal Pelvis and Ureter in Patient With Hemophilia A

Intramural renal pelvic and ureteral hemorrhage is seen most commonly in patients treated with anticoagulant therapy. However, spontaneous intramural hemorrhage of the ureter seen in patients with hemophilia is a rare entity and has been reported only in 2 cases. Computed tomography is a valuable imaging method in the diagnosis and follow-up. We report the ultrasound and computed tomography findings of spontaneous intramural renal pelvic and ureteral hemorrhage in a patient with hemophilia A.

Ovarian vein thrombosis and Mirror syndrome in association with sacrococcygeal teratoma

Ballantyne’s syndrome has originally been described for hydrops fetalis, which is associated with rhesus isoimmunization; however, hydrops fetalis can also occur in association with non-immunological causes, including Ebstein’s anomaly, Galen’s vein aneurysm, fetal arrhythmias, and sacrococcygeal teratoma (SCT). SCT is the most commonly presenting tumor in newborn babies, occurring in approximately 1 in every 40,000 live births. Large or rapidly growing tumors are highly vascular, and lead to high-output cardiac failure, which is characteristic of hydrops fetalis. In non-immune hydrops fetalis maternal preeclampsia (Mirror syndrome) can also sometimes occur. The clinical manifestations of mirror syndrome are quite varied, and the pathophysiology of this syndrome is poorly understood.1–3 Ovarian vein thrombosis (OVT) is a rare complication of pregnancy; however, recognition and treatment of this condition are critical because a delay in diagnosis can lead to significant maternal morbidity. The diagnosis of OVT remains a challenge because there is no known profile of risk factors.4 In this manuscript, we describe a case of a rapidly growing SCT that is associated with Mirror syndrome and ovarian vein thrombosis.

Diagnosis and percutaneous treatment of partial subclavian steal: Doppler ultrasonography and phase contrast magnetic resonance angiography findings and a brief review of the literature

A 66-year-old woman presented with back pain and arm claudication. Severe stenosis of the left proximal subclavian artery was detected incidentally by thorax computed tomography. Doppler ultrasonography and phase contrast magnetic resonance angiography (PCMRA) evaluation revealed partial subclavian steal. The stenosis was successfully treated with percutaneous stenting. Imaging findings are described and a brief review of the literature emphasizing the role of PCMRA in diagnosing partial steal is discussed.

Successful Off-Label Use of Recombinant Factor VIIa and Coil Embolization in an Adolescent with Massive Hemoptysis Due to Invasive Pulmonary Aspergillosis.

Invasive fungal infections have turned out to be a significant cause of morbidity and mortality in pediatric patients with malignant disorders. Massive hemoptysis, a rare complication of invasive pulmonary aspergillosis, may threaten the lives of patients, usually during the resolution of neutropenia. In this report, we describe a patient with massive hemoptysis due to invasive pulmonary aspergillosis whose bleeding was controlled successfully with off-label use of recombinant factor VIIa and subsequent coil embolization of the right pulmonary artery.

Olmesartan associated with acute renal failure in a patient with bilateral renal artery stenosis

In patients with renal artery stenosis (RAS), the inhibition of renin-angiotensin-aldosterone system can cause deterioration of renal function. Here we present a 75-year-old man who developed acute renal failure after olmesartan treatment. Following discontinuation of olmesartan, his renal functions normalized. His renal Doppler ultrasonography and renal angiography showed findings consistent with bilateral RAS. In this case, unlike those previously reported, renal failure developed with olmesartan for the first time and after only a single dose, which is thought to be a new, safe, and tolerable antihypertensive agent. This is a well-defined effect of angiotensin-converting enzyme inhibitors, in patients with RAS. Also with the increasing use of angiotensin II receptor blockers (ARBs), renal failure associated with ARBs in patients with RAS is rising. The use of olmesartan also requires caution and close follow-up of renal functions for patients who have risk factors.

Bilateral renal vein thrombosis secondary to methylene tetrahydrofolate reductase mutation: a rare case

To the Editor, Renal vein thrombosis (RVT) is a rare but serious complication that is associated with many systemic disorders [1]. Thromboembolic complications, especially RVT, are frequent in nephrotic syndrome and are very prevalent in membranous nephropathy [1]. Trauma, oral contraceptives, infection, inherited pro-coagulant defects, lupus anticoagulant, antiphospholipid syndrome and severe dehydration are the other most common causes of RVT in adults [1]. Herein, we describe bilateral RVT secondary to heterozygous methylene tetrahydrofolate reductase (MTHFR) mutation. During differential diagnosis, we wish to alert physicians that RVT may be a cause of flank pain and haematuria, even in subjects with no known risk factors for thrombosis. Because early diagnosis with appropriate treatment is associated with good prognosis, the present case highlights the importance of thrombophilic investigation in all patients with suspected RVT to avoid missing this rare but frequently curable condition. To the best of our knowledge, this is the first reported case of RVT associated with MTHFR mutation in the adult population. A 29-year-old woman was admitted to the hospital after complaining of sudden onset right flank pain. Her medical history was unremarkable and she was not using any drugs or oral contraceptives. She had one healthy 5-year-old child and no reported abortion or miscarriage. There was no family history of thrombosis. On admission, her vital signs and physical examination were normal except for right flank tenderness. Admission laboratory analyses showed haemoglobin = 10.5 g/dL (12–16 g/dL), leucocyte = 12.3 × 109/L, platelet = 515 × 109/L, mean corpuscular volume (MCV) = 73.6 fL (80–96 fL) and C-reactive protein = 16 mg/L (0–10 mg/L). Her urinalysis showed microscopic haematuria. Her renal and liver function analyses were all normal. Chest and abdominal X-rays and electrocardiogram showed nothing remarkable. Abdominal ultrasonography (US) was suspicious for thrombosis of the right and left RV without any evidence of masses or hydronephrosis. Further investigation with Doppler US revealed absence of blood flow at the right RV, total continuous thrombosis from the right RV to the vena cava inferior (VCI) and a partial thrombosis at the left RV extending to the VCI. The patient was diagnosed with bilateral RVT. After these findings were confirmed with renal venography, manual thrombus aspiration was performed and optimal restoration of bilateral RV was obtained (Figure 1). Although a partial thrombus remained because of the difficulties and risks associated with mechanical total aspiration, a selective thrombolytic treatment was planned. Continuous streptokinase infusion was given through a catheter that was placed during venography. Anticoagulant therapy was continued with enoxaparin. On the following day, control angiography showed normal contrast transition and no thrombosis. At the third day, she was advised to continue anticoagulation with warfarin. An extensive workup to determine the underlying cause was performed. Her echocardiography and thoracoabdominal computed tomography (CT) findings were normal. She had no evidence of nephrotic syndrome or glomerulonephritis. Serum folate, vitamin B12, complement, erythropoietin and homocysteine (Hcy) levels were all normal. Results for protein C and S deficiency, antinuclear antigen, anti-double-stranded DNA, lupus anticoagulant, anti-cardiolipin antibodies, antithrombin III and viral markers using blood that had been collected before anticoagulant therapy were all negative. Investigations into an underlying hereditary thrombophilia showed only heterozygous MTHRF-1298 gene mutation; a lifelong oral anticoagulant therapy with warfarin and aspirin was recommended. After 3 months, her control CT angiography showed no thrombosis in the RVs or VCI. Fig. 1 Filling defects secondary to thrombosis in the right RV and VCI (white arrows) after contrast administration from vena cava superior. Diagnosis of RVT is difficult and physicians must have high suspicion of the disease to make early diagnosis, especially in young patients without any risk factors [2]. After confirmation of RVI, a full evaluation for underlying disorders should be undertaken to direct future therapy/precautions and to obtain prognostic indications for recurrence. Treatment for RVT has evolved from nephrectomy to thrombectomy and finally to thrombolytic therapy with anticoagulation, which is currently the standard treatment of choice [1]. Here, we present a young woman with bilateral RVT. Her case constituted the first clinical report of heterozygous MTHFR mutation with RVT, which was her only risk factor for the disease. MTHFR is a key enzyme for intracellular folate homeostasis and metabolism that catalyses the reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the main circulating form of folate and the methyl donor for the vitamin B12-dependent remethylation of Hcy to methionine. Results from previous studies showed that the 677TT MTHFR genotype can be considered as an independent risk factor for both arterial and venous thrombosis and may itself increase the risk for thrombosis even in the absence of other thrombophilic risk factors [3,4]. Recently, a novel MTHFR polymorphism, 1298A3C, which changes glutamic acid into an alanine residue, was shown to be associated with decreased enzyme activity but did not result in decreased folate plasma levels or increased plasma Hcy concentrations in homozygous or heterozygous members of neural tube defect families [5]. Also, others have reported that MTHFR 1298CC and MTHFR 1298AC had no effect on the risk for vein thrombosis [6]. In contrast, we present the first adult case that shows a relation between RVT and MTHFR-1298. Conflict of interest statement. None declared.