Serkan Kahraman

Apolipoprotein E gene polymorphism in renal transplant recipients: effects on lipid metabolism, atherosclerosis and allograft function

Abstract:  Introduction:  Atherosclerosis is a serious complication and leading cause of mortality in renal transplant recipients (RTRs). Hyperlipidemia may be associated with progression of renal disease and chronic allograft dysfunction. Similarities in the pathogenesis of glomerulosclerosis and atherosclerosis have been proposed. Apolipoprotein (apo) E gene code forms three major isoforms (E2, E3, and E4) with variable effects on lipid metabolism.

Gingival health status in renal transplant recipients: relationship between systemic inflammation and atherosclerosis

Cardiovascular disease (CVD) is the leading cause of mortality in renal transplant recipients (RTR). Systemic and periodontal inflammation has been suggested to have a possible role in the development of atherosclerosis. In the present study, we aimed to investigate the relationship between gingival health status, inflammation and atherosclerosis in RTRs. Eighty‐three RTR (50 male, 33 female) were enrolled in the study. Routine biochemical analyses, serum lipoproteins, C‐reactive protein, fibrinogen, homocystein, parathyroid hormone (PTH) and cyclosporin A (CsA) trough levels were studied. All patients had 24‐h ambulatory blood pressure monitoring and B‐mode ultrasound of the common carotid arteries. Gingival status was evaluated by the Löe and Silness gingival index (GI). Mean GI value was 2.3 ± 0.5. Fifty patients (60.3%) had GI value ≥ 2.1 (severe gingivitis; group A). Thirty‐three patients (39.7%) had GI value < 2.1 (no or moderate gingivitis; group B). Age, carotid intima‐media thickness (CIMT) and mean time on dialysis before transplantation were significantly higher in group A than in B. Systemic inflammation markers were not different between group A and group B. Mean CIMT was positively correlated with GI (r = 0.425; p = 0.001) and negatively correlated with high‐density lipoprotein cholesterol (r = −0.256; p = 0.023). After the correction for confounding variables, mean CIMT was still significantly correlated with GI (r = 0.376, p = 0.02). In RTR, gingival inflammation seems to be associated with CIMT in the absence of systemic inflammation. Thus, gingivitis may, in part, play a role in the development of systemic atherosclerosis without causing any aggravation in systemic inflammatory response.

Impact of amlodipine or ramipril treatment on left ventricular mass and carotid intima-media thickness in nondiabetic hemodialysis patients

Objective: Left ventricular hypertrophy (LVH) and atherosclerosis are frequently observed in uremic patients and they have appeared as an independent predictor of cardiovascular morbidity and mortality. The aim of this study was to compare the effects of ramipril and amlodipine on left ventricular mass index (LVMI) and carotid intima-media thickness (CIMT) in nondiabetic hypertensive hemodialysis patients. Methods: A total of 112 hemodialysis (HD) patients were included in this study. Patients were randomly allocated to receive ramipril or amlodipine for 1 year. Blood pressure (BP) measurements, LVMI, and CIMT were assessed at baseline and 6-month intervals. Biochemical parameters and inflammatory markers were also determined at the initiation and during the study period. Results: Similar BP decrease was observed in treatment groups. During follow-up, LVMI and CIMT progressed likewise in both treatment groups despite BP control. However, subgrouping analyses due to the pattern of left ventricular geometry showed that LVMI in patients with eccentric LVH increased, whereas LVMI decreased in subjects with concentric LVH under antihypertensive treatment. Discussion: BP control with ramipril or amlodipine could not provide adequate protection for development or progression of atherosclerosis and eccentric type of LVH in nondiabetic HD patients.

Impact of rHuEPO therapy initiation on soluble adhesion molecule levels in haemodialysis patients.

Background:  Increased levels of soluble adhesion molecules have been reported in haemodialysis (HD) patients. Recent studies have shown that recombinant human erythropoietin (rHuEPO) elicits proliferation and migration of endothelial cells and modifies endothelial function. The present study was design to explore the effects of rHuEPO on serum levels of soluble adhesion molecules in HD patients.

Efficacy and Safety of Intravenous Iron Therapy for HCV-Positive Haemodialysis Patients

Background: Iron supplementation is the cornerstone of anaemia management in haemodialysis (HD) patients. However, efficacy and safety of intravenous (IV) iron therapy in hepatitis C virus (HCV)-positive HD patients is yet to be elucidated. Methods: Sixty-six maintenance HD patients with suboptimal response to recombinant human erythropoietin (rh-EPO) were administered IV iron. Each patient received 100 mg/session IV iron sucrose for ten consecutive HD sessions and then the dose was decreased to 50–100 mg weekly or biweekly. Patients were followed for haemoglobin (Hb), ferritin, rh-EPO dose requirements, transaminase levels, and adverse drug reactions. Results: Baseline demographic and clinical characteristics, as well as Hb, ferritin, transaminase levels, rh-EPO and iron doses were similar between HCV-positive (n = 32) and HCV-negative patients (n = 29). After 5 months of follow-up, a significant increase in ferritin and Hb levels and decrease in rh-EPO doses were observed in both groups. The incidence of adverse drug reactions was not associated with HCV serology. Significant elevation in both alanine and aspartate aminotransferase levels were detected in HCV-positive patients. Conclusion: This study has shown that IV iron administration reverses suboptimal response to rh-EPO administration in HD patients regardless of HCV serology. There is however subtle increase of transaminase levels in HCV-positive patients. Further studies are warranted to reveal the impact of variation in serum transaminase levels during IV iron administration in HCV-positive HD patients.

Impact of cytokine gene polymorphism on cardiovascular risk in renal transplant recipients

Cardiovascular events are the leading causes of morbidity and mortality in renal transplant recipients (RTR). Given the role of inflammation in atherosclerosis, the contribution of functional polymorphisms of cytokines to cardiovascular diseases (CVD) was assessed in RTR in this study. Polymorphisms of tumour necrosis factor alpha (TNF‐α) gene [−308 (G→A), −238 (G→A)], interleukin‐10 (IL‐10) gene [−1082(A→G), −819 (T→C), −592 (A→C)], transforming growth factor beta 1 (TGF‐β1) gene [codon 10 (T→C), codon 25 (G→C)], carotis intima media thickness (CIMT), left ventricular mass index (LVMI), 24‐h ambulatory blood pressure and serum lipoprotein homocysteine level, erythrocyte sedimentation rate, serum C‐reactive protein (CRP) and serum fibrinogen level of RTR were determined. Seventy‐two RTR (26 cadaveric allograft, 46 living‐related allograft, 43 male, 29 female) were included in this study. LVMI were similar in TNF‐α, IL‐10 and TGF‐β1 genotypes. Right and left CIMT were higher in TT genotype (n = 16) than CT (n = 46) and CC (n = 10) genotypes of TGF‐β1 codon 10 (T→C) gene polymorphism (RCIMT, 7.7 ± 2.2 mm vs. 7.0 ± 1.4 mm vs. 5.9 ± 1.4 mm, P = 0.025; LCIMT, 8.5 ± 2.5 mm vs. 7.0 ± 1.3 mm vs. 6.1 ± 1.2 mm, P = 0.002). Lipoprotein (a) level of TT genotype (35.5 ± 22.5 mg/dl) was higher than CC (4.1 ± 2.8 mg/dl) and CT (20.4 ± 11.2 mg/dl) genotypes of TGF‐β1 codon 10 (T→C) gene polymorphism (P = 0.037). High producers of cytokine IL‐10 −1082 [GG (n = 22) vs. AA + AG (n = 50)] and low producers of TGF‐β codon 25 [GC + CC (n = 17) vs. GG (n = 55)] had lower IMT of carotid artery but the difference did not reach statistical significance (P > 0.05). The CIMT of renal transplant patients was similar in IL‐10 (−819, −592) and TNF‐α (−308, −238) genotypes. No difference was observed in 24‐h ambulatory blood pressure levels, serum lipoproteins, plasma homocysteine level, erythrocyte sedimentation rate, serum CRP, serum fibrinogen level in IL‐10, TNF‐α and TGF‐β1 genotypes. Besides the well‐known factors, TGF‐β1 gene polymorphisms might play a role in CVD in RTR even at early stages of asymptomatic atherosclerosis.

The interleukin‐10 promoter genotype predicts diastolic dysfunction in maintenance hemodialysis patients

Interleukin‐10 (IL‐10) predominantly acts as an anti‐inflammatory factor. Polymorphisms in the IL‐10 gene promoter determine quantitative cytokine production. Doppler echocardiography and tissue Doppler imaging (TDI) are superior to conventional echocardiography to evaluate diastolic dysfunction. The IL‐10 gene promoter polymorphism at position (−1082) was studied for its association with conventional and Doppler echocardiographic and TDI parameters in 112 hemodialysis (HD) patients. Blood pressure, serum C‐reactive protein (CRP), and albumin levels were also examined for the association study. The genetic association study showed that among the HD patients, there was no difference in the prevalence of systolic and diastolic dysfunction between genotypes on conventional echocardiography. However, using Doppler echocardiography and TDI, high producers for the IL‐10 −1082 promoter (−1082/GG) have higher E velocities, E/A values, lateral, and septal E′ velocities and a lower isovolumic ventricular relaxation time than low (−1082/AA) and intermediate producers (−1082/GA). Significantly higher levels of serum CRP levels and lower plasma albumin levels were found in low and intermediate producers for the IL‐10 −1082 promoter than high producers. The IL‐10 genotype may balance the effects of inflammatory cytokines on the myocardium and may be a determinant of LV function in HD patients.