Abdullah Ozkok

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

BACKGROUND AND OBJECTIVESnVascular 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.nnnDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSnSeventy-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.nnnRESULTSnBaseline 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.nnnCONCLUSIONSnBaseline 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

BACKGROUNDnDecreased 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.nnnMETHODSnSixty-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.nnnRESULTSnThe 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.nnnCONCLUSIONSnCACS 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.

FGF-23 associated with the progression of coronary artery calcification in hemodialysis patients

BackgroundDisordered mineral metabolism is implicated in the pathogenesis of vascular calcification in hemodialysis (HD) patients. Fibroblast growth factor 23 (FGF-23) is the main regulator of phosphate metabolism. In this prospective study, we aimed to investigate the association of serum FGF-23 with progression of coronary artery calcification in HD patients.MethodsSeventy-four HD patients (36 male/38 female, mean age: 52u2009±u200914 years) were included. Serum FGF-23 levels were measured by ELISA. Coronary artery calcification score (CACS) was measured twice with one year interval. Patients were grouped as progressive (PG) (36 patients-48%) and non-progressive (NPG).ResultsAge, serum phosphorus, baseline and first year CACS were found to be significantly higher in the PG compared to NPG group. Serum FGF-23 levels were significantly higher in PG [155 (80–468) vs 147 (82–234), pu2009=u20090.04]. Patients were divided into two groups according to baseline CACS (low group, CACSu2009≤u200930; high group, CACSu2009>u200930). Serum FGF-23 levels were significantly correlated with the progression of CACS (ΔCACS) in the low baseline CACS group (ru2009=u20090.51, pu2009=u20090.006), but this association was not found in high baseline CACS group (ru2009=u20090.11, pu2009=u20090.44). In logistic regression analysis for predicting the PG patients; serum FGF-23, phosphorus levels and baseline CACS were retained as significant factors in the model.ConclusionsSerum FGF-23 was found to be related to progression of CACS independent of serum phosphorus levels. FGF-23 may play a major role in the progression of vascular calcification especially at the early stages of calcification process in HD patients.

Clinical characteristics and predictors of progression of chronic kidney disease in autosomal dominant polycystic kidney disease: a single center experience

BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease. The course and progression of the disease is highly variable. In this study, we aimed to investigate the impact of clinical characteristics and basic biochemical parameters on progression of chronic kidney disease (CKD) in ADPKD patients.Materials and methodsA total of 323 consecutive patients with ADPKD were enrolled into the study and followed with a mean duration of 100xa0±xa038xa0months. Patients were grouped as rapid progressors (RP) and slow progressors (SP) according to median rates of decline in glomerular filtration rate (ΔGFR) per year, namely 1xa0ml/min/year.ResultsHistory of macroscopic hematuria, urinary stone and smoking were more common in male patients; hepatic and other organ cysts were more common in female patients. ∆GFR/year was similar between males and females [0.95 (0–3.02) vs. 1.11 (0.10–2.74)xa0ml/min/year, pxa0=xa00.21]. History of smoking and pack-year of cigarettes smoked were significantly higher in the RP compared to the SP group (36 vs. 18xa0%, pxa0=xa00.01 and 5.24xa0±xa01.20 vs. 3xa0±xa01.32 pack-year, pxa0=xa00.02, respectively). Baseline 24xa0h-proteinuria was found to be significantly correlated with the percent decline of GFR (∆%GFR) per year (rxa0=xa00.303, 0.001). In Cox regression analysis for predicting the progression of CKD, age, hypertension, urinary stone and proteinuria were retained as the significant independent factors predicting progression of CKD in the model.ConclusionBaseline proteinuria was significantly correlated with ∆%GFR per year. Hypertension and proteinuria were found to be the major treatable risk factors for the progression of CKD in ADPKD patients.

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

OBJECTIVEnThe 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.nnnMETHODSnFifty-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.nnnRESULTSnThere 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.nnnCONCLUSIONSnElevated 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.

Lower serum prohepcidin levels associated with lower iron and erythropoietin requirements in hemodialysis patients with chronic hepatitis C

BackgroundPatients with chronic HCV infection have increased liver iron. Recently identified protein hepcidin synthesized in the liver, is thought to be a key regulator for iron homeostasis and is induced by infection and inflammation. Lower erythropoietin and iron supplementation requirements were previously reported in HD patients with HCV infection. We investigated the association of prohepcidin with inflammation and iron parameters in HD patients with and without chronic HCV infection.MethodsSixty patients (27 male, 33 female, mean age 50 ±15u2009years) on chronic HD were included. Parameters related to iron metabolism (ferritin, serum iron and total iron binding capacity (TIBC)), inflammation (hs-CRP, TNF-α and IL-6) and prohepcidin levels were measured. The response to treatment (erythropoiesis-stimulating agent (ESA) resistance index) was assessed from the ratio of the weekly erythropoietin (rhuEPO) dose to hemoglobin (Hb) per unit weight.ResultsSerum prohepcidin levels of HCV positive patients (135u2009±u200925u2009ng/mL) were significantly lower than HCV negative patients [148u2009±u200918u2009ng/mL, (pu2009=u20090.025)]. Serum IL-6 levels of HCV positive patients were also significantly lower than HCV negative patients (pu2009=u20090.016). Serum prohepcidin levels were positively correlated with ferritin (ru2009=u20090.405, pu2009=u20090.001) and IL-6 (ru2009=u20090.271, pu2009=u20090.050) levels in HD patients. In the HCV positive group, serum prohepcidin levels significantly correlated with ferritin levels (ru2009=u20090.514 pu2009=u20090.004). In the HCV negative group, serum prohepcidin levels significantly correlated with serum IL-6 levels (ru2009=u20090.418, pu2009=u20090.027). In multiple regression analysis performed to predict prohepcidin in HCV positive patients, serum ferritin was found to be an independent variable (ru2009=u20090.28, pu2009=u20090.008).ConclusionsHCV positive HD patients have low levels of serum prohepcidin and IL-6 which might account for iron accumulation together with lower iron and rhuEPO requirements in these patients.

Severe thrombocytopenia and alveolar hemorrhage represent two types of bleeding tendency during tirofiban treatment: case report and literature review

Tirofiban is a glycoprotein (GP) IIb/IIIa receptor antagonist used in the treatment of acute coronary syndrome (ACS). Thrombocytopenia is a well-known complication of GPIIb/IIIa inhibitors. Life-threatening complications such as alveolar and gastrointestinal system hemorrhages may occur in the course of thrombocytopenia. Platelet count should be monitored closely, including during the first few hours of the infusion. Adverse events may be prevented by prompt discontinuation of the therapy. Herein we present two cases of profound and sudden thrombocytopenia associated with tirofiban use in the treatment of ACS together with a review of the literature.

QT dispersion predicts mortality and correlates with both coronary artery calcification and atherosclerosis in hemodialysis patients.

PurposeQT dispersion (QTd) was shown to be an independent predictor of mortality in hemodialysis (HD) patients. It may be hypothesized that coronary artery calcification is related to QTd in HD patients because widespread calcification may also involve the cardiac conducting system in these patients. In this study, we aimed to investigate the relationships of corrected QTd (QTcd) with coronary artery calcification score (CACS), carotid plaque score (CPS) and possible influence of these parameters on survival of HD patients.MethodsSeventy-two HD patients (33 male, 39 female) were enrolled into the study. Mean age of the patients was 44xa0±xa012xa0years. Mean follow-up duration was 77xa0±xa024xa0months. CACS was determined by computed tomography. QTcd values were calculated as the difference of maximum and minimum QT intervals. Left ventricular mass index (LVMI) and CPS were measured by echocardiography.ResultsQTcd was significantly correlated with CACS (rxa0=xa00.233, pxa0=xa00.049), CPS (rxa0=xa00.354, pxa0=xa00.003) and LVMI (pxa0=xa00.011, rxa0=xa00.299). CPS was found to be significantly higher in the group with high QTcd (>60xa0ms) [2 (1–4) versus 0 (0–1), pxa0=xa00.02]. CACS was significantly correlated with age (rxa0=xa00.44, pxa0<xa00.001), LVMI (rxa0=xa00.52, pxa0<xa00.001) and CPS (rxa0=xa00.32, pxa0=xa00.003). In Kaplan–Meier analysis, survival of patients with high QTcd was significantly lower than the patients with low QTcd. In Cox regression analysis for predicting mortality, age, serum albumin and QTcd were found to be the independent predictors of mortality.ConclusionsQTcd independently predicted mortality, and it was significantly associated with coronary artery calcification, left ventricular hypertrophy and atherosclerosis in HD patients.

Elevated resistin levels are associated with inflammation in hemodialysis patients with failed renal allografts

Background Resistin is an adipocytokine, associated with insulin resistance and inflammation. The aim of this study is to evaluate the levels of serum resistin levels and other markers of inflammation in hemodialysis (HD) patients with failed renal allografts. Methods Sixty-nine HD patients with failed renal allografts and 98 never transplanted (naive) HD patients and also 21 healthy controls were included in the study. Serum levels of various biochemical parameters as well as resistin, IL-6, TNF-α and hs-CRP as biochemical markers of inflammation, were measured. Results Serum resistin levels in patients with failed renal allografts (4.80 ± 2.06 ng/mL) were significantly higher than those of the naive HD patients (3.44 ± 1.48 ng/mL) and healthy controls (0.95 ± 0.38 ng/mL; p<0.001). Patients with failed transplants were also characterized by higher TNF-alpha levels (96.8 ± 131.3 pg/mL vs. 40.9 ± 25.4 pg/mL; p<0.001) and IL-6 levels (83.9 ± 150.9 pg/mL vs. 14.6 ± 14.4 pg/mL; p<0.001) as compared to naive HD patients. Serum hs-CRP levels in patients with failed renal allografts (9.33 ± 11.86 mg/L) were significantly higher than those of the naive HD patients (1.26 ± 1.71 mg/L) and healthy controls (2.12 ± 1.82 mg/L; p<0.001). Serum albumin levels in patients with failed transplants (3.84 ± 0.47 g/dL) were lower as compared to never transplanted HD patients (4.13 ± 0.33 g/dL) and healthy controls (4.53 ± 0.40 g/dL; p<0.001). There was a positive correlation between serum resistin and TNF-alpha levels (r = 0.486, p<0.001). Conclusions Serum resistin levels are increased in HD patients with failed renal allografts very probably reflecting an allograft-induced chronic inflammatory state.

Cystatin C is better than albuminuria as a predictor of pulse wave velocity in hypertensive patients

Abstract Introduction: Arterial stiffness is important in the evaluation of the cardiovascular risk in both general population and hypertensive patients. In this study, we aimed to investigate the associations of both serum cystatin C levels and albuminuria with arterial stiffness in healthy controls and hypertensive patients. Patients and methods: Seventy-six healthy controls (male/femaleu2009=u200944/32) and 76 hypertensive patients (male/femaleu2009=u200943/33) were enrolled. Arterial stiffness parameters such as augmentation index (AIx) and pulse wave velocity (PWV) were non-invasively measured with the Arteriograph (Tensiomed Ltd., Budapest, Hungary). Results: AIx (31.92u2009±u200914.31 vs. 27.95u2009±u200911.03, pu2009=u20090.03) and PWV (9.84u2009±u20091.62 vs. 8.87u2009±u20092.04, pu2009<u20090.001) were significantly higher in hypertensive patients compared to healthy controls. Patients with microalbuminuria had significantly higher AIx (43.47u2009±u20099.91 vs. 30.37u2009±u200914.13, pu2009=u20090.002) and higher serum cystatin C levels [0.76 (0.67–0.95) vs. 0.68 (0.62–0.78) mg/L, pu2009=u20090.03]. In the hypertensive group, AIx was significantly correlated with PWV (ru2009=u20090.519, pu2009<u20090.001), glomerular filtration rate (cystatin C) (ru2009=u2009–0.438, pu2009=u20090.003), mean arterial pressure (MAP) (ru2009=u20090.288, pu2009=u20090.015) and urinary albumin–creatinine ratio (ACR) (ru2009=u20090.386, pu2009=u20090.004). PWV was associated with serum cystatin C (ru2009=u20090.442, pu2009=u20090.003) and MAP (ru2009=u20090.377, pu2009=u20090.001). In the linear regression analysis (model ru2009=u20090.577, pu2009=u20090.006) for the prediction of PWV in hypertensive patients, MAP, urinary ACR, age and serum cystatin C levels were included as independent variables. Cystatin C was found to be the significant determinant of PWV in hypertensive patients. Conclusion: Multivariate analysis revealed that serum cystatin C but not albuminuria was significantly associated with PWV in hypertensive patients. Serum cystatin C may be better than albuminuria as a predictor of arterial stiffness in hypertensive patients.