Yasar Caliskan

Efficacy of anakinra treatment in a patient with colchicine-resistant familial Mediterranean fever

Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by self-limited recurrent attacks of fever and serositis. The serious complication of FMF is AA-type amyloidosis, which can result in end-stage renal disease. Although colchicine is effective in the majority of patients, there is no established treatment for those who are resistant or intolerant to colchicine. We herein report the efficacy of anakinra in a 52-year-old Turkish patient with FMF, secondary amyloidosis and renal transplant, who was resistant to colchicine treatment.

Reduction of uric acid levels with allopurinol treatment improves endothelial function in patients with chronic kidney disease.

BACKGROUND Endothelial dysfunction (ED) is a key event in the development of atherosclerotic cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). Association of hyperuricemia with CVD has been previously reported in the nonuremic population. In this prospective study, we aimed to evaluate the effects of treatment of hyperuricemia with allopurinol on ED and changes in the serum reactive oxygen species in patients with CKD. METHODS In this study, 19 (13 male) hyperuricemic (UA > 7 mg/dl) nondiabetic CKD patients without any comorbidity, aged < 60 years with creatinine clearance (CrCl) between 20 and 60 ml/min were evaluated. Endothelial functions were assessed by ischemia-induced forearm vasodilatation method (EDD). Oxidative stress was evaluated by measuring the serum oxidized LDL (ox-LDL), advanced oxidation protein products (AOPP) and nitrotyrosine (NT) levels. After measuring all these tests at baseline, allopurinol therapy was commenced for 8 weeks. After 8 weeks of allopurinol treatment, all measurements were repeated. Then, allopurinol treatment was ceased and same measurements were also repeated 8 weeks after ceasing of the treatment. RESULTS Serum creatinine, total cholesterol, albumin, hs-CRP, CrCl and proteinuria levels of the patients were similar among three study periods. After allopurinol therapy, the mean serum UA and NT levels significantly reduced as compared to baseline. At the 8th week after cessation of allopurinol treatment, serum UA levels were significantly increased. After allopurinol therapy, EDD value increased from 5.42 ± 8.3% at baseline to 11.37 ± 9% (p < 0.001). At the 8th week after ceasing allopurinol treatment, EDD returned to baseline values (5.96 ± 8%, p < 0.001). CONCLUSION Treatment of hyperuricemia with allopurinol improve ED in patients with CKD. However, mechanism responsible for this beneficial effect seems to be apart from antioxidant effects of allopurinol.

Extrapulmonary tuberculosis in immunocompetent adults

Tuberculosis continues to be a significant cause of morbidity and mortality. Although tuberculosis usually attacks the lungs, other organs can also be affected, leading to extrapulmonary tuberculosis (EPT) or disseminated tuberculosis. This study retrospectively analysed the incidence, clinical sites and risk factors for EPT in 252 patients with EPT between 1 January 1991 and 30 June 2003. EPT was defined as clinical, laboratory, imaging, and/or histopathological evidence of mycobacterial infection in a site other than hilar lymph nodes or lung parenchyma. In our study group, tuberculous lymphadenitis (36.5%) was found to be the most common clinical presentation of EPT. 119 (47.2%) patients developed the severe form of EPT, according to the WHO report, and 133 (52.8%) patients developed the less severe form. A case history of pulmonary tuberculosis was found to be a risk factor for the development of EPT (p<0.05). The study showed that EPT is still a public health problem. These findings suggested that pulmonary tuberculosis may play a critical role in the development of EPT. 12-month therapy may be chosen in patients with EPT considering acceptable adverse effects without relapses.

Osteoprotegerin/RANKL Axis and Progression of Coronary Artery Calcification in Hemodialysis Patients

BACKGROUND AND OBJECTIVES Vascular calcification is associated with increased cardiovascular mortality in chronic hemodialysis patients. This prospective study investigated the relationship between serum osteoprotegerin, receptor activator of NF-κB ligand, inflammatory markers, and progression of coronary artery calcification score. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Seventy-eight hemodialysis patients were enrolled. Serum IL-1β, IL-6, TNF-α, osteoprotegerin, receptor activator of NF-κB, fetuin A, and bone alkaline phosphatase were measured by ELISA. Coronary artery calcification score was measured two times with 1-year intervals, and patients were classified as progressive or nonprogressive. RESULTS Baseline and first-year serum osteoprotegerin levels were significantly higher in the progressive than nonprogressive group (17.39±9.67 versus 12.90±6.59 pmol/L, P=0.02; 35.17±18.35 versus 24±11.65 pmol/L, P=0.002, respectively). The ratio of serum osteoprotegerin to receptor activator of NF-κB ligand at 1 year was significantly higher in the progressive group (0.26 [0.15-0.46] versus 0.18 [0.12-0.28], P=0.004). Serum osteoprotegerin levels were significantly correlated with coronary artery calcification score at both baseline (r=0.36, P=0.001) and 1 year (r=0.36, P=0.001). Importantly, progression in coronary artery calcification score significantly correlated with change in serum osteoprotegerin levels (r=0.39, P=0.001). In addition, serum receptor activator of NF-κB ligand levels were significantly inversely correlated with coronary artery calcification scores at both baseline (r=-0.29, P=0.01) and 1 year (r=-0.29, P=0.001). In linear regression analysis for predicting coronary artery calcification score progression, only baseline coronary artery calcification score and change in osteoprotegerin were retained as significant factors in the model. CONCLUSIONS Baseline coronary artery calcification score and serum osteoprotegerin levels were significantly associated with progression of coronary artery calcification score in hemodialysis patients.

Coronary artery calcification and coronary flow velocity in haemodialysis patients

BACKGROUND Decreased coronary flow reserve (CFR) is a marker of endothelial dysfunction, coronary artery calcification and inflammation, well-known cardiovascular risk factors in haemodialysis (HD) patients. In this study, we aimed to investigate the correlation of coronary artery calcification scores (CACS) with CFR in HD patients. METHODS Sixty-four end-stage renal failure patients were enrolled in this study (38 males, 26 females). Thirty-nine healthy subjects (22 males, 17 females) were included in the control group. Biochemical parameters and acute-phase inflammation marker [high-sensitivity C-reactive protein (hs-CRP)] of patients were recorded before dialysis. The CACS were measured by electron beam computerized tomography method. CFR recordings were performed by trans-thoracic Doppler echocardiography. The relationship between CACS and CFR was evaluated. RESULTS The mean CACS was 281 +/- 589 and 29 patients had CACS < 10. Patients with CACS > 10 had significantly lower CFR values compared to patients with CACS < 10 (1.56 +/- 0.38 vs 1.84 +/- 0.53, P = 0.024). However, there was no difference in hs-CRP values between the groups. CFR was negatively correlated with CACS (r = -0.276, P = 0.030). In multiple stepwise regression analysis, CACS was found to be an independent variable for predicting CFR (P = 0.048). During a follow-up of 18 months, 10 patients had experience of cardiovascular events. Patients with CACS > 10 had significantly higher event rate [34.5% (10/29) vs 0% (0/24)] compared to those with CACS < 10 (P = 0.001). Patients who developed cardiovascular events had significantly higher mean CACS and lower CFR values than the remaining group (P = 0.019 and P = 0.039). All of four patients who died during follow-up were in the CFR < 2 and CACS > 10 groups. CONCLUSIONS CACS was associated with CFR in HD patients. However, we did not find any association of inflammation with CACS and CFR. This association between CFR and CACS might indicate two different (anatomical and functional) aspects of the common pathophysiology of the arterial system in HD patients.

Appetite-regulating Hormones in Chronic Kidney Disease Patients

OBJECTIVE Inflammation and loss of appetite is the most common problem in patients with chronic kidney disease (CKD). This comparative cross-sectional study aimed to characterize the changes in circulating levels of ghrelin, obestatin, leptin, all of which have an effect on food intake, and proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) in patients with CKD who were undergoing different treatments. DESIGN AND SETTING Study participants included 36 patients who had undergone hemodialysis (body mass index [BMI]: 22.3 ± 4.17 kg/m(2)); 41 who had undergone peritoneal dialysis (BMI: 23.5 ± 3.10 kg/m(2)), 30 with early stage CKD (BMI: 24.4 ± 3.32 kg/m(2)), and 31 healthy subjects (24.3 ± 2.14 kg/m(2)). The patients with CKD were kept under a standard diet with restricted salt, potassium, and protein intake. INTERVENTION Levels of leptin, acylated ghrelin, obestatin, TNF-α, and IL-6 were measured by commercially available enzyme-linked immunosorbent assay kits. Total nitrite/nitrate was analyzed using colorimetric assay kit. RESULTS Significantly high leptin levels, accompanied by low acylated ghrelin levels, were observed in patients with CKD. Maintenance dialysis did not affect these levels. TNF-α and IL-6 levels were significantly higher in CKD patients than in healthy subjects, the highest being in dialysis patients. Obestatin levels were relatively low in patients who had undergone hemodialysis. CONCLUSION Low acyl-ghrelin levels, accompanied with high levels of TNF-α and IL-6 may be involved in the loss of appetite and poor nutritional status in CKD patients.

Coronary flow reserve dysfunction in hemodialysis and kidney transplant patients

Abstract: Background:  The assessment of coronary flow reserve (CFR) by trans‐thoracic echocardiography has recently been introduced into clinical studies. Impairment of coronary microvascular functions and decreased CFR detected by trans‐thoracic Doppler harmonic echocardiography (TTDE) has recently been reported in hemodialysis (HD) patients, but there is no comparative study between HD patients and renal transplant recipients.

Hepatitis C virus infection in hemodialysis patients is not associated with insulin resistance, inflammation and atherosclerosis.

BACKGROUND Hepatitis C virus (HCV) infection is associated with increased levels of inflammatory markers and is also a significant risk factor for the development of Type 2 diabetes mellitus (DM) in the general population. In attempt to address this issue in chronic hemodialysis (HD) patients, we evaluated the relation of HCV infection with inflammatory markers, endothelial dysfunction, insulin resistance and atherosclerosis. METHODS In a cohort of 72 HD patients (36 (50%) had a positive HCV EIA test and 36 (50%) had a negative anti-HCV test), we examined HCV antibody status, insulin resistance (HOMA-IR) and beta-cell function (HOMA-beta), serum inflammatory parameters (high sensitive C-reactive protein (CRP), fibrinogen and procalcitonin), and performed echocardiography, high-resolution brachial artery ultrasound and B-mode carotid Doppler examination to assess the vascular functions and atherosclerosis. RESULTS There were no differences in age, gender, body mass index (BMI), primary disease, duration of dialysis, smoking status, laboratory parameters except glucose, total cholesterol and LDL cholesterol between anti-HCV-positive and anti-HCV-negative groups. The serum concentrations of glucose, total cholesterol and LDL cholesterol were significantly lower in the anti-HCV-positive patients than anti-HCV-negative patients (p = 0.04, p = 0.02, p = 0.01, respectively). There were no significant differences in inflammatory parameters, total insulin secretion (HOMA-beta, p = 0.76) and insulin resistance (HOMA-R, p = 0.91) between anti-HCV-positive and negative patients. The intima media thickness, carotid plaque score and brachial artery endothelium-dependent dilatation did not differ significantly between the two groups (p = 0.44, 0.45, and 0.17, respectively). CONCLUSION HCV infection was not related to atherosclerosis and insulin resistance in hemodialysis patients. Since hemodialysis patients had a large number of uremia-related cardiovascular risk factors, the effect of HCV infection could disappear in this group of patients.

Association between chronic hepatitis C infection and coronary flow reserve in dialysis patients with failed renal allografts.

BACKGROUND Hepatitis C infection occurs frequently among patients with end-stage renal disease and increases the risk of atherosclerotic cardiovascular diseases. Endothelial dysfunction (ED) is an early event in the pathogenesis of atherosclerosis. It has been reported among patients treated with hemodialysis (HD), peritoneal dialysis (PD), or renal transplantation. The aim of the present study was to evaluate effects of chronic hepatitis C infection on ED in patients with failed renal transplants. METHODS Twenty-six nondiabetic, anti-hepatitis C virus (HCV)-positive (15 females, mean age: 38 +/- 8 years) and 26 anti-HCV-negative patients (15 females, mean age: 36 +/- 5 years), all of whom had returned to PD or HD after renal transplant failure were studied to assess coronary flow reserve (CFR) by transthoracic Doppler echocardiography. Serum high-sensitivity C-reactive protein (hs-CRP) levels were measured as markers of chronic inflammation. CFR recordings and intima-media thickness measurements were performed using the Vivid 7 echocardiography device. RESULTS Demographic and clinical characteristics of patients were similar between the two groups. Serum hs-CRP levels were significantly higher among HCV-positive patients versus HCV-negative counterparts. HCV-positive patients showed lower CFR measurement than HCV-negative ones. Also, a negative correlation was observed between serum hs-CRP levels and CFR values. CONCLUSION CFR values are worse among anti-HCV-positive patients with failed renal transplants compared with anti-HCV-negative subjects. Graft dysfunction per se may aggravate a proinflammatory states thereby inducing ED. Furthermore, the presence of HCV is a greater trigger of ED among patients with renal failed grafts.

Comparison of markers of appetite and inflammation between hemodialysis patients with and without failed renal transplants.

OBJECTIVE The survival of patients returning to hemodialysis (HD) following kidney transplant failure is unfavorable. However, the factors responsible for this poor outcome are largely unknown; chronic inflammation due to failed allograft and malnutrition may contribute to morbidity and mortality. We aim to compare the markers of appetite and malnutrition, and their relation with inflammation in HD patients with and without previous kidney transplantation. METHODS Fifty-six patients with failed renal allografts at least 3 months on dialysis (31 men, 25 women; mean age, 46 ± 9 years) and 77 HD patients who never underwent a transplant (43 men, 34 women; mean age, 50 ± 15 years) were included in the study. The appetite and diet assessment tool (ADAT) was used to determine the self reported appetite of patients. Serum concentrations of ghrelin, leptin, insulin like growth factor 1 (IGF-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) were measured. Associations among these variables were analyzed. RESULTS There were no significant differences considering age, gender or duration of renal replacement therapy between the 2 groups. The scores from Appetite and Diet Assessment Tool were significantly higher in the failed-transplant group. Serum ghrelin levels were significantly higher and serum albumin levels were significantly lower in the failed-transplant group. Serum leptin levels were similar between 2 groups. In addition, hs-CRP, IL-6, and TNF-α levels, which were used as inflammatory parameters, were significantly higher in the failed-transplant group. CONCLUSIONS Elevated serum ghrelin levels and inflammation may cause diminished appetite and malnutrition in patients with failed renal allografts, and higher levels of this hormone seem to be associated with inflammation caused by retained failed allografts.