Normalization of endothelial dysfunction following renal transplantation is accompanied by a reduction of circulating visfatin/NAMPT. A novel marker of endothelial damage?

Abstract:  Endothelial dysfunction is strongly linked to cardiovascular disease and outcome of patients with chronic kidney disease. We hypothesized that decreased inflammatory activity and increased adiponectin following transplantation could be one mechanism for a better endothelial health. Fifty-eight living donor kidney transplant non-diabetic recipients, 31 (23 male, 29 ± 5 yr) on cyclosporine A and 27 (10 male, 26 ± 5 yr) on tacrolimus immunsupression, were studied longitudinally. Visfatin, adiponectin, high sensitive C-reactive protein (hsCRP) levels, brachial artery flow mediated dilatation (FMD) and nitroglycerine mediated dilatation were measured before transplantation and on the 30th and 90th day after transplantation. Pre-transplantation visfatin, adiponectin and FMD values of patients were significantly higher than those of the controls (p < 0.001 for all). All values decreased significantly 30 and 90 d post-transplantation. Plasma visfatin and adiponectin, correlated negatively with FMD levels 90 d both before and after kidney transplantation (p < 0.001 for both). Endothelial function improved during the first month after transplantation, and the degree of improvement correlated to reductions in circulating visfatin, adiponectin and hsCRP levels. Of interest, the intracellular enzyme visfatin was the strongest predictor of FMD both before and after kidney transplantation and may thus reflect endothelial cell damage directly.     

Increased serum renalase in hemodialysis patients: is it related to left ventricular hypertrophy?

Introduction: Left ventricular hypertrophy (LVH) is one of the most common cardiac abnormalities in patients with end stage renal disease (ESRD). Hypertension, diabetes, increased body mass index, gender, age, anemia, and hyperparathyroidism have been described as risk factors for LVH in patients on dialysis. However, there may be other risk factors which have not been described yet. Recent studies show that renalase is associated with cardiovascular events. The aim of this study was to reveal the relation between renalase, LVH in patients under hemodialysis (HD) treatment.

Methods: The study included 50?HD patients and 35 healthy controls. Serum renalase levels and left ventricle mass index (LVMI) were measured in all participants and the relation between these variables was examined.

Findings: LVMI was positively correlated with dialysis vintage and C-reactive protein (CRP) (r?=?0.387, p?=?0.005 and r?=?0.597, p?r?=??0.324, p?=?0.022 and r?=??0.499, p?r?=?0.263, p?=?0.065). Serum renalase levels were significantly higher in HD patients (212?±?127?ng/mL) compared to controls (116?±?67?ng/mL) (p?r?=?0.677, p?r?=?0.625, p?Discussion: In our study, LVMI was correlated with dialysis vintage, residual diuresis, CRP, and hemoglobin. LVMI tends to correlate with renalase and this correlation may be significant in studies with more patient numbers. The main parameters affecting renalase levels are dialysis vintage and serum creatinine.     

Adiponectin level is reduced and inversely correlated with the degree of proteinuria in type 2 diabetic patients

AIMS: Adiponectin seems to be an important modulator for metabolic and vascular diseases. We aimed to measure plasma adiponectin levels in type 2 diabetic patients and investigate any association with the severity of proteinuria. METHODS: 80 patients (mean age, 46.9 +/- 5.1 years; body mass index (BMI), 25.8 +/- 1.98 kg/m2) and 47 healthy volunteers (mean age, 46.1 +/- 5.5 years; BMI 26.74 +/- 2.23 kg/m2) were included. Plasma adiponectin concentration, insulin levels, homeostasis model assessment (HOMA) indices, calculated glomerular filtration rate (GFR), high sensitive C reactive protein (hsCRP) and biochemistry panel were determined in all subjects. The association between adiponectin concentration and proteinuria was evaluated. Additionally, the relationship between adiponectin and hsCRP and calculated GFR were also investigated. RESULTS: Adiponectin levels in patients were significantly lower than those of controls (n = 80; 8.76 +/- 4.50 microg/ml for patients, n = 47; 24.27 +/- 5.59 microg/ml for controls, p < 0.001). Plasma adiponectin levels in patients with proteinuria were significantly lower than those without proteinuria (n = 43; 6.81 +/- 2.82 microg/ml for proteinuria, n = 37; 11.98 +/- 3.32 microg/ml for no proteinuria, p < 0.001). There was a significant negative correlation between plasma adiponectin concentrations and the degree of proteinuria (r = -0.433, p < 0.001). There were also significant negative correlations between adiponectin concentrations and insulin levels as well as HOMA index in the patient group (r = -0.322, p = 0.004; r = -0.301, p = 0.032). Additionally there was a significant negative correlation between adiponectin and hsCRP levels in the patient group (r = -0.872, p < 0.001). CONCLUSION: The results show that adiponectin is lower in patients with type 2 diabetes and the levels are negatively correlated with the severity of proteinuria.     

Relationship between sleep complaints and proinflammatory cytokines in haemodialysis patients

BACKGROUND: Sleep complaints are common in end-stage renal disease. We aimed to investigate the relationship between sleep-related complaints and inflammatory cytokines in haemodialysis (HD) patients, and also the effects of HD on sleep patterns and cytokine levels. METHODS: Predialysis serum interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) levels in nine patients with sleep complaints were compared with those of nine patients without sleep complaints and nine healthy controls. Patients with sleep complaints underwent polysomnography the night after HD and the following night. RESULTS: Patients with sleep complaints had significantly higher predialysis IL-1beta levels compared with those without and healthy controls (P=0.004 and P=0.000, respectively). They also had higher predialysis IL-6 and TNF-alpha levels than those without sleep complaints; however, the difference was not significant. Patients without sleep complaints had higher mean IL-6 and TNF-alpha and similar mean IL-1beta levels compared with healthy controls (P=0.001, P=0.024, P=0.26, respectively). Obstructive sleep apnoea syndrome (OSAS) was found in six out of nine (66%) patients with sleep complaints. Sleep architecture and cytokine levels did not differ between the two nights. The mean serum IL-1beta, IL-6 and TNF-alpha levels did not differ in the pre- and post-polysomnographic samples. There was no correlation between IL-1beta, IL-6 or TNF-alpha levels and the apnoea-hypopnoea index. CONCLUSIONS: Proinflammatory cytokines, IL-1beta in particular, might be associated with sleep complaints in HD patients. OSAS is not uncommon in HD patients with sleep-related complaints and sleep architecture does not appear to be effected by the HD procedure itself.     

The spectrum of diseases causing fever of unknown origin in Turkey: a multicenter study.

OBJECTIVE: The purpose of this trial was to determine the spectrum of diseases with fever of unknown origin (FUO) in Turkey. METHODS: A prospective multicenter study of 154 patients with FUO in twelve Turkish tertiary-care hospitals was conducted. RESULTS: The mean age of the patients was 42+/-17 years (range 17-75). Fifty-three (34.4%) had infectious diseases (ID), 47 (30.5%) had non-infectious inflammatory diseases (NIID), 22 (14.3%) had malignant diseases (MD), and eight (5.2%) had miscellaneous diseases (Mi). In 24 (15.6%) of the cases, the reason for high fever could not be determined despite intensive efforts. The most common ID etiologies were tuberculosis (13.6%) and cytomegalovirus (CMV) infection (3.2%). Adult Still's disease was the most common NIID (13.6%) and hematological malignancy was the most common MD (7.8%). In patients with NIID, the mean duration of reaching a definite diagnosis (37+/-23 days) was significantly longer compared to the patients with ID (25+/-12 days) (p=0.007). In patients with MD, the mean duration of fever (51+/-35 days) was longer compared to patients with ID (37+/-38 days) (p=0.052). CONCLUSIONS: Although infection remains the most common cause of FUO, with the highest percentage for tuberculosis, non-infectious etiologies seem to have increased when compared with previous studies.     

Short term fluvastatin treatment lowers serum asymmetric dimethylarginine levels in patients with metabolic syndrome

Elevated concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, are associated with endothelial dysfunction. Metabolic syndrome (MetS) is also a condition associated with impaired endothelial function. To test the hypothesis that lipid lowering treatment with a statin lowers ADMA levels, we investigated the effect of fluvastatin treatment on serum ADMA levels in patients with MetS. A total of 85 hypercholesterolemic MetS patients (53 females, 32 males; mean age, 55.8+/-9.1 years) were included in this prospective, randomized, controlled study. Patients were randomly assigned to either the treatment (n=42) or control group (n=43). Recommendations for lifestyle modification were provided to both groups. In addition, the patients in the treatment group received fluvastatin, extended release tablets, 80 mg/day, orally for 6 weeks. Serum levels of ADMA and lipids were assessed at baseline and at the completion of treatment. High performance liquid chromatography was used to measure serum ADMA concentrations. In the fluvastatin group, there was a significant reduction in serum ADMA levels compared to baseline (from 1.57+/-1.07 micromol/L to 1.17+/-1.41 micromol/L, P<0.05), whereas in the control group no significant change was observed (from 1.06+/-0.46 micromol/L to 1.24+/-1.38 micromol/L, P>0.05). There was a statistically significant difference between the groups in terms of mean percent change from baseline (P=0.047). Fluvastatin treatment for hypercholesterolemia in patients with MetS is associated with a decrease in serum ADMA levels at 6 weeks. This finding is consistent with known beneficial effects of statin treatment on endothelial function in hypercholesterolemic patients.     

Topical N-Acetylcysteine Improves Wound Healing Comparable to Dexpanthenol: An Experimental Study

In this study, we aimed to compare the effects of dexpanthenol and N-acetylcysteine on wound healing. The wound healing process is a multifaceted sequence of activities associated with tissue restoration process. A number of investigations and clinical studies have been performed to determine new approaches for the improvement of wound healing. A total of 30 rats were divided into 3 equal groups. A linear 2-cm incision was made in the rats'' skin. No treatment was administered in the first (control) group. Dexpanthenol cream was administered to the rats in the second group and 3% N-acetylcysteine cream was administered to the rats in the third group. The wound areas of all of the rats were measured on certain days. On the 21st day, all wounds were excised and histologically evaluated. The epithelialization and granulation rates between the groups were revealed to be similar in microscopic evaluations. Although the fibrosis was remarkable in the control group as compared with the other groups, it was similar in N-acetylcysteine and dexpanthenol groups. Angiogenesis rate was remarkable in the N-acetylcysteine group compared with the others. In multiple-comparison analysis, Dexpanthenol and N-acetylcysteine groups had similar results in terms of wound healing rates (P < 0.05), which were both higher than in the control group (P > 0.05). The efficacy of N-acetylcysteine in wound healing is comparable to dexpanthenol, and both substances can be used to improve wound healing.Key words: N-acetylcysteine, Dexpanthenol, Wound healingWound healing is a multifaceted sequence of activities associated with the tissue restoration process.¹ This activity takes place in 4 main steps: inflammation, proliferation, matrix deposition, and remodeling.^2,3 Moreover, there are many factors that might have harmful effects on the wound healing process. In this regard, there have been numerous analyses and clinical studies aiming to find new methods for the improvement of wound healing processes.⁴Dexpanthenol is the biologically-active alcohol of pantothenic acid, which leads to an elevation in the amount of coenzyme A in the cell. Dexpanthenol is extensively used in topical form, since it can easily penetrate the skin even at large local concentrations. When used in formulations, dexpanthenol is most effective for the stimulation of epithelialization, granulation, and the mitigation of itching.⁵N-acetylcysteine (NAC) is a prodrug that supplies bioavailable cysteine for glutathione replenishment and prevents oxidative damage as well as inflammation. It also leads to glutathione (GSH) formation in the body. Besides fostering angiogenesis, it is used to scavenge free radicals. NAC has a number of functions in the stages of repair process, including cell proliferation, migration, and scratch wound healing. Moreover, NAC has also been reported to promote wound healing in diabetic rats.⁶In this study, we aimed to compare the effects of dexpanthenol, a molecule that is widely used to improve wound healing, and NAC, a molecule that reduces oxidative stress and inflammation, on wound healing.