Risk Factors for Erythrocytosis in Renal Transplantation: Is Ganciclovir Therapy One of Them?

BACKGROUND The purpose of this study was to identify the prevalence and risk factors of post-transplant erythrocytosis (PTE) and its relationship with cytomegalovirus (CMV). MATERIAL AND METHODS The study consisted of patients who received a kidney allograft and followed-up in our nephrology transplantation clinic from 2000 to 2014. Patient age, sex, length of dialysis, etiology of end-stage kidney disease, date of transplantation, medications, types of donors, the development of PTE were recorded. RESULTS Among 185 adult kidney recipients, 43 (23.2%) had PTE. The average time between transplantation and diagnosis was 36 months. PTE was more common in male patients (P<0.05) and patients with living donors and those who had been treated with ganciclovir after transplantation (P<0.05). There were 79 patients treated for CMV - 54 in the non-PTE group and 24 in the PTE group. There was no significant difference in patient age, etiology of end-stage kidney disease, and immunosuppressive therapy when comparing the PTE group and non-PTE group. Univariate analysis showed ganciclovir therapy was significantly associated with PTE. However, this was not seen in the multivariate analyses. CONCLUSIONS Treatment with ganciclovir can precipitate development of PTE. Prospective studies are needed to assess the association of between PTE and CMV infection, valganciclovir, and ganciclovir.

Protective effect of beta-glucan on contrast induced-nephropathy and a comparison of beta-glucan with nebivolol and N-acetylcysteine in rats.

BACKGROUND: It has been shown that beta-glucan (BG), which has antioxidant and immunomodulatory effects, attenuats renal ischemia-reperfusion injury. We aimed to investigate whether BG might have a preventive role against the development of contrast-induced nephropathy and to compare its effect with nebivolol (Nb) and N-acetylcysteine (NAC). METHODS: Thirty-six Wistar albino female rats were randomly divided into six groups (n = 6 each): control, contrast media (CM), BG, BG + CM, Nb + CM, and NAC + CM. With the exception of control and CM groups, the others were given drugs orally once a day for 5 days. Kidney function parameters, inflammatory parameters, and serum and renal tissue oxidative stress markers were measured. RESULTS: Increases of serum creatinine and blood urea nitrogen levels were significantly higher (p < 0.05) in the CM group only. Absolute changes of serum creatinine levels in BG, BG + CM and Nb + CM groups were significantly lower than those in the CM group (p < 0.05). Serum levels of advanced oxidation protein products and malondialdehyde were significantly less (p < 0.05) in the BG group compared to the CM group. Histopathological lesions in the CM group were more advanced (p < 0.05). No significant differences between the BG + CM, Nb + CM and NAC + CM groups were found with regard to histopathological findings. CONCLUSION: This study suggests that BG protects or ameliorates against contrast-induced nephropathy. Its beneficial effects may be similar to or greater than those of Nb or NAC.

A case of an accelerated uremic neuropathy.

We present a 62-year-old man, with a prior history of diabetes mellitus, atherosclerotic heart disease, and chronic renal failure requiring peritoneal dialysis, who developed accelerated uremic sensorimotor polyneuropathy. Our patient significantly improved after effective hemodialysis. Although renal transplantation is a curable therapy for uremic neuropathy, effective dialysis is still an important treatment for the group of patients who cannot undergo renal transplantation.

Association of the angiotensinogen M235T and APO E gene polymorphisms in Turkish type 2 diabetic patients with and without nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is a leading cause of diabetes-related morbidity and mortality. The aim of this study was to evaluate the relationship of AGT M235T and apoprotein E (APO E) gene polymorphism with DN in Turkish patients of Type 2 diabetes, and to compare genotype and allele distributions among DN patients, non-DN patients, and healthy controls. METHODS: AGT M235T and APO E genotype and allele analysis were performed in 111 DN patients, 108 non-DN patients, 106 healthy control subjects for APO E genotype, and 100 for AGT M235T genotype polymorphism. APO E and AGT M235T genotype were determined by RFLP-PCR. RESULTS: The frequencies of APO E ε2/3, ε 3/3, ε 3/4 genotypes were 22.7%, 60%, 60%, respectively, among DN patients and 6.6%, 80%, 10.4%, respectively (p < 0.001), in the non-DN patients. The frequencies of AGT M235T MM, MT, TT genotypes among the same groups were 17%, 46%, 37% and 21%, 63%, 16%, respectively (p < 0.02). Having the ε2/3 genotype and TT genotype increased the risk for DN nephropathy [4.8-fold (95% CI: 1.94-11.67), 2.9-fold (95% CI: 1.27-6.69), respectively]. CONCLUSION: Our study has shown that AGT M235T TT genotype and APO E ε 2/3 genotype may be linked to a risk for DN among Turkish population.

TCF7L2 (rs7903146) But Not CDKAL1 (rs7754840) Gene Polymorphisms Increase the Risk of New-Onset Diabetes After Kidney Transplant.

OBJECTIVES: Incidence of new-onset diabetes after transplant negatively affects graft and patient survival. Obesity, impaired fasting glucose before transplant, and a history of diabetes in first-degree relatives are well-defined risk factors. TCF7L2 and CDKAL1 gene polymorphisms have been implicated in the pathogenesis. We investigated the effect of single gene polymorp-hisms of TCF7L2 (rs7903146) and CDKAL1 (rs7754840) on new-onset diabetes in renal transplant recipients. MATERIALS AND METHODS: We evaluated 239 renal transplant recipients. TCF7L2 and CDKAL1 gene polymorphisms were assessed by polymerase chain reaction. RESULTS: Mean patient age was 43 ± 13 years. There were 148 male patients (61.9%), and 91 were female (38.1%). New-onset diabetes was detected in 55 patients (23%). In 20 cases (36%), the glycemic disorder was transient; 61% of patients required insulin therapy. In terms of CDKAL1, 108 patients had the wild-type allele, 112 had a single-allele mutation, and 19 had a 2-allele mutation (45.2%, 46.9%, and 7.9%, respectively). In terms of TCF7L2, 163 of the patients had the wild-type allele, 49 had a single-allele mutation, and 27 had a 2-allele mutation (68%, 20%, and 11%, respectively). New-onset diabetes-related factors were age at transplant, body mass index after transplant (calculated as weight in kilograms divided by height in meters squared), tacrolimus, mycophenolate, and TCF7L2 polymorphism but not CDKAL1 polymorphism. After multiple regression analysis, the effect of TCF7L2 polymorphism persisted. A single allelic change resulted in a risk factor 1.4 times higher for new-onset diabetes after transplant (P = .043; 95% CI, 1.142-1.874) and a double allelic change was 2.7 times higher (P < .01; 95% CI, 1.310-4.073) Conclusions: TCF7L2 (rs7903146) gene polymorphism is an independent risk factor for new-onset diabetes in Turkish renal transplant patients. This study is the first in Turkey to show the distribution and effect of these genes in kidney transplant patients.

Risk Factors for Posttransplant Erythrocytosis: Parathyroid Hormone Paradox?

OBJECTIVES: Posttransplant erythrocytosis affects 8% to 26% of kidney transplant recipients. In this study, our aim was to define associations among hypercalcemia, persistent hyperparathyroidism, and posttransplant erythrocytosis. We also investigated the effects of biologic sex, age, and dialysis modality before transplant on posttransplant erythrocytosis development. MATERIALS AND METHODS: We enrolled 247 patients [159 (64%) male and 88 (36%) female] who underwent kidney transplant between 2009 and 2018. All demographic and laboratory parameters were retrospectively analyzed as possible factors associated with posttransplant erythrocytosis. RESULTS: Fifty-nine (24%) of total patients had posttransplant erythrocytosis. The median time to posttransplant erythrocytosis development was 16 months (range, 8-34 mo). Male sex, the use of peritoneal dialysis as maintenance renal replacement therapy before kidney transplant, and persistent hyperparathyroidism were defined as independent risk factors for posttransplant erythrocytosis development in our multivariate logistic regression analyses (odds ratio = 5.228, 3.963, and 4.109, respectively). In addition, high serum creatinine levels were associated with a lower incidence of posttransplant erythrocytosis (odds ratio = 0.253). Although significance did not remain after multivariate analysis, hypercalcemia was found to be significantly associated with posttransplant erythrocytosis in univariate analyses (odds ratio = 1.768). In subgroup analyses, where only male patients were evaluated, persistent hyperparathyroidism and peritoneal dialysis were found to be independent risk factors for posttransplant erythrocytosis development (odds ratio = 4.176 and 5.003). CONCLUSIONS: Persistent hyperparathyroidism and hypercalcemia could precipitate development of posttransplant erythrocytosis. The preserved residue renal function may be associated with increased endogenous erythropoietin, which could lead to posttransplant erythrocytosis development.

Oral Candida Colonization as a Risk Factor for Chronic Inflammation and Atherosclerosis in Hemodialysis Patients.

The purpose of this study was to determine the prevalence of oral Candida spp. in HD patients and to investigate its relation with systemic inflammation and atherosclerosis. Microbiological samples were taken from buccal mucosa, palate, and dental prosthesis with a cotton swab. High-sensitivity CRP (hsCRP) and IL-6 were measured as inflammation markers. A total of 69 patients (58% male and median age 62 years) were enrolled in this study; 53.6% of total patients had oral Candida colonization. HsCRP and IL-6 levels were found to be significantly higher in the oral Candida colonization positive group than in the Candida colonization negative group (P = 0.002 and P = 0.01, respectively). HDL levels were significantly lower in the Candida colonization positive group (P = 0.03). Peripheral artery disease (P = 0.05) and oral Candida colonization (P = 0.002) were significantly associated with inflammation. In addition to conventional risk factors such as age (P = 0.03), diabetes (P = 0.001), and peripheral artery disease (P = 0.002), oral Candida colonization is associated with coronary artery disease (P = 0.04). Oral Candida colonization might be associated with chronic inflammation and development of atherosclerosis in HD patients.

Is survival enough for quality of life in Sagliker Syndrome-uglifying human face appearances in chronic kidney disease?

BACKGROUND: It is known that secondary hyperparathyroidism (SH) and particularly skeletal changes is a severe condition in chronic kidney disease (CKD). Sagliker syndrome (SS) is a very prominent feature in CKD including uglifying human face appearances, short stature, extremely severe maxillary and mandibulary changes, soft tissues in the mouth, teeth-dental abnormalities, finger tip changes and severe psychological problems. METHODS: In the last 8 years we have confronted 36 extremely incredible SS cases in CKD by performing an international study in Turkey, India, Malaysia, Romania and Egypt. RESULTS: In addition to the uglifying human face appearance, we found extremely severe X-ray and tomographical, pantomographical, histo-pathological changes in the head and whole body. Finally, we compared previous face pictures with recent ones. Just a few years earlier they had been pretty and good-looking young boys and girls. By investigating their history, we understood they had not received proper therapy and were in the late-irreversible period. CONCLUSION: SS is a serious and severe complication of CKD. Late and improper treatment leads to abnormalities throughout skeleton particularly in the skull and face. Changes particularly in children and teens become irreversible-disastrous for appearance and psychological health. Appropriate treatment must begin as early as possible in specialized centers. It is possible that SS patients may survive long-term with dialysis, but with all those particular changes could anyone claim this type of life would continue in an acceptable way without extending their height, correcting all the changes in the skull and face, remodeling new faces and most particularly convincing the patients to deal with all those tragi-dramatic psychological problems?

International study on Sagliker syndrome and uglifying human face appearance in severe and late secondary hyperparathyroidism in chronic kidney disease patients.

OBJECTIVE: It is known that skeletal changes due to secondary hyperparathyroidism (SH) can be severe in chronic kidney disease (CKD). Recently described Sagliker syndrome (SS) is a very striking and prominent feature of SH in CKD, including an uglifying appearance to the face, short stature, extremely severe maxillary and mandibulary changes, soft tissue in the mouth, teeth/dental abnormalities, fingertip changes, knee and scapula deformities, hearing abnormalities, and neurological and, more important, severe psychological problems. DESIGN, SETTING, PATIENTS: In the past 8 years, we have encountered 40 cases of SS in SH and CKD by performing an international study in Turkey, India, Romania, Egypt, Maleysia, Tunis, and China. RESULTS: The medical history of these patients showed that they did not receive proper therapy. Changes, particularly in children and teenagers, become irreversible, which was disastrous for the patients both aesthetically and psychologically. CONCLUSION: Treatment must begin early and be the appropriate treatment given in centers with sophisticated skills. Otherwise, the inability to correct all the changes in the skull and face, to remodel a new face, to extending the height, and, most important, to convince the patients to face the dramatic psychological problems can be catastrophic for those patients.

The relationship of visfatin levels to inflammatory cytokines and left ventricular hypertrophy in hemodialysis and continuous ambulatory peritoneal dialysis patients.

Visfatin was recently defined as an adipocytokine; however, the pathophysiological role of visfatin is not completely understood. A few studies suggest that visfatin may be a new proinflammatory adipocytokine. The aim of the present study was to compare serum visfatin levels between hemodialysis and continuous ambulatory peritoneal dialysis (CAPD) patients and evaluate the relationship between visfatin levels to IL-6, TNF-alpha, and left ventricular hypertrophy. Serum visfatin, IL-6, and TNF-alpha levels were measured by using the ELISA method, and echocardiographic evaluations were performed in 31 hemodialysis patients, 30 CAPD patients, and 21 healthy volunteers. Serum visfatin levels were higher in the CAPD group (265.27 +/- 387.86 ng/mL) than hemodialysis (97.68 +/- 244.96 ng/mL,) and control (41.33 +/- 48.87 ng/mL) groups (p = 0.04, p = 0.01, respectively). No significant difference was observed between the hemodialysis and control groups. In univariate analysis, visfatin levels were positively correlated with IL-6 (r = 0.24, p = 0.03), TNF-alpha (r = 0.34, p = 0.002), and BMI (r = 0.26, p = 0.03) and negatively correlated with some left ventricular diastolic parameters [Em and Em/Am (r = -0.305, p = 0.01), (r = -0.251, p = 0.03), respectively]. No relationship was found between visfatin and left ventricular mass index. In the linear regression analysis, visfatin levels independently related with TNF-( (beta = 0.369, p = 0.001) and IL-6 (beta = 0.284, p = 0.015). This study has found significantly higher levels of serum visfatin in CAPD patients when compared to healthy individuals. Increased visfatin levels seem to associate with proinflammatory cytokines such as IL-6 or TNF-alpha. As for the effects of on left ventricular structure and functions, visfatin might have negative effects on left ventricular diastolic function parameters but have no effects on left ventricular mass index.

The relationship among asymmetric dimethylarginine (ADMA) levels, residual renal function, and left ventricular hypertrophy in continuous ambulatory peritoneal dialysis patients.

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial-based nitric oxide synthase. Its level is increased by end stage renal disease. However, most studies showing an increase in ADMA in dialysis patients have focused on hemodialysis. Results with peritoneal dialysis patients have been more inconclusive. Recent studies suggest that ADMA may be a new cardiovascular risk factor. The aim of the present study was to evaluate the relationship between ADMA levels, residual renal function, and left ventricular hypertrophy in peritoneal dialysis patients. Serum ADMA measurements and echocardiographic evaluations were performed in 54 peritoneal dialysis patients and 26 healthy volunteers. Residual renal function was measured in peritoneal dialysis patients by urea clearance from a urine collection. Thirty-two of the 54 peritoneal dialysis patients had residual renal function. ADMA levels of the peritoneal dialysis group were found to be significantly higher than those of healthy individuals (p = 0.03). Within the peritoneal dialysis group, ADMA levels of patients with residual renal function were significantly lower than those without residual renal function (p = 0.01), though they were still higher than the ADMA levels of the control group (p = 0.04). Serum levels of ADMA were positively correlated with left ventricular mass index (r = 0.29, p = 0.01) and negatively correlated with early mitral inflow velocity (Em) (r = -0.28, p = 0.01), Em/Late mitral inflow velocity (Am) (r = -0,32, p = 0.00), and isovolumetric relaxation time (r = -0.30, p = 0.01). In conclusion, increased ADMA levels seem to be associated with left ventricular hypertrophy in peritoneal dialysis patients, and residual renal function may lead to a reduction of serum ADMA levels.

Prognostic value of troponin T and homocysteine in patients with end-stage renal disease.

OBJECTIVES: The most important cause of increased mortality in end-stage renal disease (ESRD) is cardiovascular diseases. We investigated the prognostic value of cardiac troponin T (cTnT) and homocysteine in the long-term follow-up of ESRD patients. STUDY DESIGN: The study included 78 patients (54 males, 24 females; mean age 53.2+/-16.6 years) with ESRD, who had been on hemodialysis treatment for at least three months. Baseline troponin T and homocysteine levels were measured and the patients were followed-up from March 2002 to May 2007 for major adverse cardiovascular events (MACE). RESULTS: Major adverse cardiovascular events occurred in 26 patients (33.3%), including cerebrovascular events (n=3, 3.9%), congestive heart failure (CHF) (n=18, 23.1%), coronary artery disease (CAD) (n=19, 24.4%), and death (n=19, 24.4%). Two-thirds of diabetic patients developed MACE and the mean age in the MACE group was significantly greater (p<0.001). Troponin T levels were significantly higher in patients who developed MACE (0.21+/-0.43 ng/ml vs 0.06+/-0.28 ng/ml, p=0.002), whereas homocysteine levels did not differ significantly between the two groups (p=0.82). For a cutoff value of 0.10 ng/ml, cTnT was > or =0.1 ng/ml in 17 patients (21.8%), and <0.10 ng/ml in 61 patients (78.8%). Patients having a cTnT level of > or =0.10 ng/ml showed significantly higher rates of MACE (64.7% vs 24.6%; p=0.003), CHF (47.1% vs 16.4%; p=0.02), and death (52.9% vs 16.4%; p=0.004). There was also a greater tendency to CAD in this group (41.2% vs 19.7%, p=0.10). In multivariate logistic regression analysis, age and diabetes mellitus were the independent predictors of MACE development. CONCLUSION: Homocysteine levels cannot predict MACE in ESRD patients in the long-term follow-up. Despite a significantly higher incidence of MACE in patients with high cTnT levels, cTnT was not an independent predictor of cardiovascular outcome.

Cod liver oil supplementation improves cardiovascular and metabolic abnormalities in streptozotocin diabetic rats.

Abnormalities in the metabolism of essential fatty acids and the results of increased oxidative stress have been implicated in cardiovascular disorders observed in diabetes mellitus. This study, therefore, aimed to investigate the effects of cod liver oil (CLO, Lysi Ltd, Iceland), which comprises mainly an antioxidant vitamin A, n:3 polyunsaturated fatty acids (n:3 PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on cardiovascular abnormalities in streptozotocin (STZ)-diabetic rats. Two days after single STZ (55 mg kg(-1), i.p.) or vehicle injection, diabetes was verified by increased blood glucose, and non-diabetic and diabetic rats were left untreated or treated with CLO (0.5 mL kg(-1) daily, by intragastric probing) for 12 weeks. Plasma glucose, triacylglycerol and cholesterol concentrations were significantly elevated in 12-week untreated-diabetic rats; CLO provided better weight gain, entirely prevented the plasma lipid abnormalities, but partially controlled the glycaemia in diabetic rats. In isolated aorta rings, diabetes resulted in increased phenylephrine-induced vasoconstriction and isoprenaline-induced vasorelaxation, impaired endothelium-dependent vasodilatation and unchanged responsiveness to sodium nitroprusside. CLO treatment completely prevented endothelial deficiency, partly corrected the phenylephrine-induced vasoconstriction and did not affect the responses to isoprenaline and sodium nitroprusside in diabetic aorta. Diabetes also produced a marked decrease in the rate of spontaneously beating right atria and a significant increase in basal contractile force of left ventricular papillary muscle. The responsiveness of right atria to the positive chronotropic effect of isoprenaline was significantly decreased in diabetic rats, and was increased in CLO-treated diabetic rats. The positive chronotropic effect of noradrenaline was markedly increased in diabetic atria, but prevented by CLO treatment. Diabetes also resulted in an increased positive inotropic response of papillary muscle to both noradrenaline and isoprenaline, which were prevented by CLO treatment. CLO treatment also resulted in lower tissue sensitivity (pD(2)) to these agonists in diabetic papillary muscle. Ventricular hydroxyproline content was found to be unchanged among the experimental groups. The ultrastructure of diabetic myocardium displayed various degenerations (i.e. intracellular oedema, myofibrillar fragmentation, condensed pleomorphic mitochondria, thick capillary irregular basement membrane, swollen endothelial cells), which were partially prevented by CLO treatment. We conclude that the supplementation with CLO is effective in preventing cardiovascular disorders observed in experimental diabetes.

Brain natriuretic peptide correlates with troponin T in patients with renal failure.

OBJECTIVES: In patients with chronic renal failure, the main cause of mortality is cardiovascular disease. Cardiac troponin T (cTnT) and brain natriuretic peptide (BNP) are found to be related with decreased survival in both the normal population and in patients with chronic renal failure in different studies. Our aim is to investigate the relationship between cTnT and BNP in patients with chronic renal failure. METHODS AND RESULTS: 58 chronic haemodialysis patients were enrolled prospectively for the study. Blood samples for measurement of cTnT and BNP were collected after the haemodialysis. The patients are divided into 3 groups according to cTnT measurements. Group I included the patients with cTnT < 0.05 ng/ml, Group II included the patients with cTnT between 0.05 and 0.1 ng/ml and group III included the patients with cTnT > 0. 1 ng/ml. We performed echocardiography in all patients to measure the left ventricular ejection fraction and thickness of septum and posterior wall. When BNP levels were compared among the 3 groups, we found that the BNP level was lowest in group I and highest in group III (165.13 +/- 125.44 pg/dl; 236.0 +/- 107.83 pg/dl; 280.71 +/- 153.25 pg/dl, respectively) (P = 0.01).The difference in BNP levels among groups was statistically significant and independent from left ventricular hypertrophy, left ventricular ejection fraction and volume overload in multiple regression analysis. We also searched the relationship between plasma cTnT and BNP levels and found a positive correlation (r = 0.3; P = 0.023). CONCLUSION: cTnT and BNP levels were related to each other in patients with chronic renal failure.These parameters can help to identify the patients with a high risk for cardiovascular diseases.

Procalcitonin and conventional markers of inflammation in peritoneal dialysis patients and peritonitis.

OBJECTIVES: To determine the significance of a newly described marker of inflammation procalcitonin (PCT), and to investigate its relationship to conventional markers of inflammation, such as C-reactive protein (CRP), fibrinogen, and erythrocyte sedimentation rate (ESR), in patients on peritoneal dialysis (PD) and with peritonitis. DESIGN: A prospective, observational clinical study. SETTING: The Nephrology Division of a University-affiliated teaching hospital. PATIENTS AND METHODS: 51 consecutive patients on PD were included in the study. Of this number, 16 developed peritonitis during the observational period. Baseline PCT, CRP, and fibrinogen concentrations and ESR of 51 PD patients were determined at a time point (TB) prior to any evidence of infection. These results were compared with laboratory values from 74 hemodialysis patients and 34 nonuremic control subjects. All PD patients then were followed prospectively for evidence of peritonitis. In addition to routine blood tests, including hemoglobin and leukocyte count, and routine biochemical tests, blood samples were taken to measure PCT, CRP, and fibrinogen concentrations and ESR at the time (T0) when patients first were diagnosed with PD peritonitis and also on the 4th (T4) and the 14th (T14) days after treatment for peritonitis was initiated. PCT was assayed by immunoluminometry. RESULTS: No significant difference was observed between baseline median serum PCT concentrations in PD and hemodialysis patients; however, in both groups, baseline median PCT concentrations were significantly higher than those of nonuremic controls (p < 0.05). The 16 patients on PD who developed peritonitis had 21 PD peritonitis episodes during the study period. The increased PCT concentration observed at T0 in PD peritonitis episodes decreased with therapy, and this change was statistically significant (p < 0.05). In a receiver operating characteristic curve analysis for peritonitis, the area under the curve (AUC) for PCT was 0.80, which was significantly lower than the AUC for CRP and greater than the AUCs for fibrinogen and ESR. The sensitivity of PCT for peritonitis was lower than the sensitivity of conventional markers of inflammation; however, the specificity of PCT was higher. CONCLUSIONS: Median serum PCT concentration in PD patients was significantly higher than in nonuremic controls but not hemodialysis patients. Serum PCT concentrations may serve as a useful adjunct to traditional markers of inflammation in detecting and monitoring inflammation and peritonitis in PD patients.

Association between neopterin and carotid intima-media thickness in hemodialysis patients.

BACKGROUND: Atherosclerotic lesions are heavily infiltrated by macrophages. Neopterin can be used as a marker of the activity of macrophages. Serum neopterin levels were elevated in non-renal patients with atherosclerosis. The intima-media thickness (IMT) of the carotid arteries in hemodialysis patients was significantly higher than in control subjects. In this study, we measured serum neopterin levels in hemodialysis patients and evaluated a possible correlation between neopterin levels and carotid IMT. PATIENTS AND METHODS: Thirty-seven hemodialysis patients (26 male/11 female, mean age 47 +/- 15 years) and 12 healthy subjects (8 male/4 female, mean age 43 +/- 10 years) were included in this study. Serum neopterin levels were measured by using a commercial ELISA kit. Carotid IMT of the subjects were measured by high-resolution B-mode ultrasonography. RESULTS: Carotid IMT values were 1.04 +/- 0.29 and 0.77 +/- 0.25 mm in hemodialysis patients and healthy controls, respectively (p < 0.01). Serum neopterin levels were 110.9 +/- 19.1 and 3.8 +/- 2.3 ng/ml in hemodialysis patients and healthy controls, respectively (p < 0.01). Serum neopterin levels were 103.2 +/- 21.3 ng/ml in hemodialysis patients with IMT < 1 mm (n = 15), and 116.7 +/- 15.4 ng/ml in hemodialysis patients with IMT > or = 1 mm (n = 22) (p < 0.05). Moreover, there was a significant correlation between serum neopterin levels and carotid IMT (p < 0.05, r = 0.363). CONCLUSION: Our findings suggest that neopterin could be associated with the severity of carotid atherosclerosis in hemodialysis patients.

Effects of amifostine on glycerol-pretreated rabbit kidneys.

Glycerol-induced acute renal failure is an experimental model for myoglobinuric nephropathy. Amifostine is a cytoprotective agent which scavenges the free radicals. Since there is enhanced production of reactive oxygen metabolites in glycerol-induced acute renal failure, we wanted to examine whether amifostine has a protective role against vascular reactivity and histological changes in kidneys isolated from glycerol-pretreated rabbits. Perfusion pressure was recorded from kidneys obtained from rabbits injected with glycerol 3 hr before the experiments and from glycerol-pretreated and non-pretreated rabbits injected with amifostine 30 min. before the experiments. Acetylcholine-induced (10(-8)-10(-5) M) vasodilatation was tested following the construction of submaximal vasoconstriction by phenylephrine. Histological investigation was performed using light microscope. Acetylcholine-induced vasodilatation was found to be significantly decreased in glycerol, glycerol+amifostine and amifostine groups compared to controls at all concentrations. Reduction in acetylcholine-induced vasodilation was more prominent in amifostine group compared to amifostine+glycerol group. There was histological renal damage in all experimental groups and this damage was more pronounced in glycerol+amifostine group. In conclusion, contrary to expectation, amifostine per se led to histological damage and potentiated the histological damage caused by glycerol and produced a decrease in acetylcholine-induced vasodilatation. The mechanisms by which amifostine exerts its effects are not known.

The effect of vitamin E supplementation on antioxidant enzyme activities and lipid peroxidation levels in hemodialysis patients.

BACKGROUND: This study has been undertaken to investigate the possible alterations of oxidant/antioxidant status in uremic patients undergoing hemodialysis (HD) and the effects of vitamin E supplementation. METHODS: Erythrocyte antioxidant enzyme activities [glutathione peroxidase (GSHPx), superoxide dismutase (SOD) and catalase (CAT)] and thiobarbituric acid reactive substance (TBARS) concentrations as a measure of lipid peroxidation in HD patients have been determined and compared with healthy controls. The patient group consisted of 36 uremic patients 21-75 years of age undergoing maintenance HD three times weekly for an average of 41 months. The efficiency of Vitamin E therapy in dialysis patients was also assessed by re-evaluating antioxidant status of the same patients after supplementation of the vitamin E in a dosage of 600 mg/daily for 14 weeks. RESULTS: A significant decrease in the activities of erythrocyte SOD, CAT and GSHPx and a significant increase in TBARS concentrations were found in patient group compared to control group (p<0.001). A significant correlation between GSHPx activities and duration of HD therapy was also observed (r=-0.46, p<0.01). Vitamin E supplementation caused an increase in GSHPx and SOD activities and a decrease in TBARS concentrations. A slight but not significant increase in CAT activity was also observed by Vitamin E. CONCLUSIONS: The results suggest the presence of an oxidative activity and the possible preventive role of Vitamin E therapy in uremic patients undergoing HD.

Increased plasma nitrate levels in patients with crush syndrome in the Marmara earthquake.

BACKGROUND: Crush syndrome has been described as extensive muscle damage, leading to acute renal failure. The aim of this study was to evaluate the possible role of nitric oxide, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) in crush syndrome. PATIENTS AND METHODS: A total of 17 patients suffering from crush syndrome, 7 patients without crush syndrome and 10 healthy controls were enrolled in the study. Plasma nitrate, TNF-alpha, IL-1 beta levels and biochemical parameters were measured. RESULTS: All patients with crush syndrome demonstrated acute renal failure. Plasma nitrate levels were elevated significantly in the crush syndrome patients compared with patients without crush syndrome (33.5 +/- 20.1 vs. 15.3 +/- 5 micromol/l, p=0.014). There was no significant difference in TNF-alpha and IL-1 beta levels between control and patient groups. CONCLUSION: Increased plasma nitrate levels in the crush syndrome may be related either to the elevated production of NO or the diminished excretion of nitrate or both.

Assessment of DNA strand breakage by the alkaline COMET assay in dialysis patients and the role of Vitamin E supplementation.

Although the role of reactive oxygen species (ROS) in chronic renal failure (CRF) is not definitely demonstrated, a consistent number of observations has provided evidence for the presence of oxidative stress in uremic patients undergoing maintenance dialysis. In order to investigate this hypothesis further and to understand the role of antioxidant supplementation, peripheral blood lymphocytes were taken from 36 dialysis patients before and after Vitamin E supplementation in a dosage of 600 mg per day (2x300 mg) for 14 weeks and examined in the alkaline Comet assay for DNA strand breakage. The results were also compared with those of 36 controls with comparable age, sex, and smoking habits, and with no history of renal disease. The DNA breakage observed in the lymphocytes of patients before Vitamin E supplementation was significantly higher than in the controls (P<0.001) but a clear protective effect of Vitamin E supplementation were observed after 14 weeks of therapy.