Serum tumor markers in advanced stages of chronic kidney diseases.

Chronic kidney disease (CKD) is one of the most important noncommunicable diseases. Abnormal concentration of some tumor markers were found in a spectrum of nonmalignant diseases such as benign ovarian tumors, breast diseases, chronic hepatitis, cirrhosis, diseases of the bile duct, and in CKD. Hence, the present study was undertaken to evaluate carbohydrate antigen (CA) 15-3, carcinoembryonic antigen (CEA), CA 19-9, and human chorionic gonadotropin (HCG) concentrations in advanced stages of CKD (Stage 4 and 5) patients who are not on dialysis and with no known malignancy. Patients included 40 CKD patients and 40 healthy controls. CA 15-3, CEA, CA 19-9, and HCG in serum were estimated by enzyme-linked immunosorbent assay method. The differences in tumor marker levels between the controls and advanced stages of CKD (Stage 4 and 5) were assessed using one-way analysis of variance using the Statistical Package for the Social Sciences for Windows version 16.5. CKD patients had significantly elevated levels of CEA, HCG, CA 19-9, and CA 15-3 compared to the control group (P = 0.001). There was no difference in the tumor markers levels between CKD Stage 4 and 5. Elevation in serum tumor markers may be a possibility in patients with CKD even in the situations of the absence of a malignancy. This may be due to an alteration in their metabolism in CKD and reduction of glomerular filtration rate leading to impaired excretion. Hence, it may be prudent to exercise caution in the interpretation of serum tumor markers as a representative for underlined malignancy in patients of CKD.

Study of contrast-induced oxidative stress in nondiabetic patients undergoing coronary angiography.

Administration of iodinated contrast media is associated with serious complications such as acute kidney injury (AKI). Oxidative stress is implicated as a major mechanism underlying the production of contrast-induced AKI (CI-AKI). There are very few human studies on oxidative stress occurring after contrast administration. Twenty-seven patients scheduled for coronary angiography were recruited. An average of 22.2 mL low-osmolal nonionic contrast was administered. Plasma conjugated dienes (CD), lipid hydroperoxides (LOOH), malondialdehyde (MDA), protein carbonyl (PC), protein thiols (PTs), ferric reducing ability of plasma (FRAP), erythrocyte super oxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase were estimated before, 30 min, 2 and 4 h after contrast administration. CD, LOOH, MDA, and PC increased (P <0.001), whereas PTs, FRAP, SOD, CAT (P <0.001), and GPx (P = 0.013) decreased in the first 4 h. Estimated glomerular filtration rate (eGFR) showed inverse association with MDA and positive association with GPx. The study provides evidence for oxidative stress following contrast administration even in the absence of predisposing factors. Association of eGFR with MDA and GPx indicate kidney as the source of oxidative stress. Hence, antioxidant therapy before contrast administration helps to prevent the development of oxidative stress, thereby reducing the risk of CI-AKI.

Changes in the inflammatory and oxidative stress markers during a single hemodialysis session in patients with chronic kidney disease.

BACKGROUND: Cardiovascular disease (CVD) is a common cause of morbidity and mortality in end-stage renal disease (ESRD) patients on hemodialysis (HD) among whom it is 5-20 times higher than in the general population. Some of the nontraditional risk factors such as oxidative stress and inflammation are related to the progress of CVD in HD patients. Several, but not all studies, reported that inflammatory and oxidative stress markers are increased during a single session of HD, mimicking changes that occur during acute immune activation. This study was taken up to evaluate the changes in the inflammatory and oxidative stress markers during a single HD session in patients with chronic kidney disease. METHODS: Twenty-five ESRD patients on maintenance HD and 25 controls were included in the study. Blood samples were obtained from the patients before starting of hemodialysis (pre-HD) and after completion of hemodialysis (post-HD). The changes in serum Pentraxin-3, hs-CRP, malondialdehyde (MDA) and ferric reducing ability of plasma (FRAP) levels were measured in pre- and post-HD ESRD patients and compared with healthy control group. RESULTS: This study found increased levels of Pentraxin-3, hs-CRP, MDA, and decreased level of FRAP in HD patients compared to controls. CONCLUSIONS: Hemodialysis procedure contributes to inflammation and oxidative stress.

Ischemia-modified albumin levels in overt and subclinical hypothyroidism.

BACKGROUND: Free radical-mediated oxidative stress (OS) has been implicated in the pathogenesis of thyroid disorders. The ischemia-modified albumin (IMA) has been proposed as a marker of protein oxidative damage, which has been found to reflect hypoxic stress. AIM: Our aim was to evaluate IMA, malondialdehyde (MDA), and reduced glutathione (GSH) levels in patients with overt hypothyroidism (OHT) and subclinical hypothyroidism (SHT) in comparison to euthyroid controls. SUBJECTS AND METHODS: Albumin, IMA, IMA/albumin ratio, MDA, GSH, total cholesterol (TC), triglycerides (TG), HDL-Cholesterol were assessed in 105 subjects grouped into OHT, SHT patients, and euthyroid controls with 35 subjects in each group. RESULTS: MDA and IMA levels were significantly elevated while the GSH concentrations were significantly lower in OHT and SHT patients compared to controls (p < 0.01). When IMA values were normalized for albumin concentrations, the IMA/albumin ratio was also significantly elevated in both patient groups compared to controls (p < 0.01). These changes were more pronounced in the OHT group when compared to SHT group. In OHT group, thyroid-stimulating hormone (TSH) levels showed significant positive correlation with MDA (r = 0.470, p = 0.004), IMA (r = 0.530, p = 0.001), and IMA/albumin ratio (r = 0.525, p = 0.001). Both IMA (r = -0.342, p = 0.041), IMA/albumin ratio (r = -0.378, p = 0.023) showed significant negative correlation with GSH in OHT patients. No significant correlation between variables was, however, observed in SHT group. CONCLUSIONS: Increase of MDA and IMA levels with decreased antioxidant status indicate the presence of OS in hypothyroid patients, which was more pronounced in OHT patients. Elevated levels of IMA can be a clinically useful marker of protein oxidative damage and OS in hypothyroidism.

Antioxidant defense in overt and subclinical hypothyroidism.

Oxidative stress as a result of disequilibrium between free radical generation and antioxidant status has been implicated in several pathologies including thyroid diseases. Studies on antioxidant status in overt (OHT) and subclinical hypothyroidism (SHT) are controversial and limited. The aim of this study was to determine the effect of OHT and SHT on antioxidant status. Thirty-six patients with OHT, 36 patients with SHT, and 39 healthy euthyroid subjects as the control group were included in the study. Plasma levels of malondialdehyde (MDA), reduced glutathione (GSH) and total antioxidant capacity (TAC) as ferric reducing ability of plasma (FRAP), and erythrocyte antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), SOD/GPx ratios, catalase (CAT), and glutathione reductase (GR) were analyzed in all groups. MDA and GPx values were elevated, while GSH, FRAP, SOD, and SOD/GPx ratio were decreased in both patient groups compared with controls. No change in activities of CAT and GR were observed in both the patient groups. Significant differences were observed between OHT and SHT groups with high MDA, GPX and low GSH, FRAP, SOD, and SOD/GPx ratio in OHT group. Thus, hypothyroid patients have a deficient antioxidant defense in the form of decreased activity of SOD, decreased levels of FRAP and GSH along with an increase in GPx activity. The severity of the disease appears to decide the degree of deficiency and our findings also point to this, in the form of decrease in SOD, FRAP, and GSH observed being more in OHT than in SHT patients. Hormonal changes and increased lipid peroxidation, which also vary with severity of disease, appear to contribute to the antioxidant deficiency.

Lipid abnormalities, lipoprotein (a) and apoprotein pattern in non-dialyzed patients with chronic kidney disease.

The present study was carried out to explore the altered lipid, lipoprotein and apoprotein abnormalities along with lipoprotein (a) in chronic kidney disease patients with stage I to V which were further divided into group 1 (stage I and II), group 2 (stage III and IV) and group 3 (stage V). 50 chronic kidney disease patients with stage I to V and 20 healthy normal subjects as controls were recruited for this study. Among the various parameters tested triglyceride levels were high in group 1 and 2, whereas VLDL cholesterol, Lp (a) and apo B levels were significantly high in all the groups when compared to controls (P<0.05). However, LDL cholesterol level was significantly low in group 3 only as compared to control group (P<0.05). Apoprotein AI values also showed significant decrease in all groups as compared to controls (P<0.05). Though total cholesterol levels in group 1 and LDL levels in group 1 and 2 were higher than controls, but the values attained not statistically significant (P>0.05). In conclusion high levels of VLDL cholesterol, Lp (a), apo B and low levels of apoprotein AI as reported in this study are the major lipid disorders in the development of cardiovascular complications at all the stages in these patients.

Carotid intima-media thickness in patients with end-stage renal disease.

Accelerated atherosclerosis and cardiovascular disease are major causes of morbidity and mortality in patients of end-stage renal disease. Carotid intima media thickness is taken as a useful surrogate marker of atherosclerosis. Thirty end-stage renal disease (ESRD) patients were subjected to ultrasonography to study CIMT before the initiation of dialysis. CIMT was found to be higher in ESRD patients than in controls. Levels of a serum marker of oxidative stress were also found to be higher in patients than in the controls. CIMT is an easy, noninvasive, reproducible, and cost-effective investigation in patients with chronic renal failure.

Association of serum antioxidants and risk of coronary heart disease in South Indian population.

BACKGROUND AND AIM: Higher prevalence of coronary heart disease (CHD) has been reported in south Indian population, which cannot be accounted for by the traditional risk factors like hyperlipidemia. Identification of new risk factors may help in treatment and prevention of CHD in this part of the world. In an attempt to investigate the causes of increased incidence of CHD in this part of the world, we intended to look for oxidative stress in our patients as a possible risk factor. As an initial step in this perspective, a case- control study was conducted to find out the serum antioxidant levels and their association with CHD in south Indian population. SETTINGS AND DESIGN: A tertiary care hospital; Case--control study. MATERIALS AND METHODS: One hundred thirty nine angiographically proven CHD patients (aged 29-75 years) were studied against 59 population based healthy controls (aged 29-72 years) free of CHD. Fasting serum cholesterol, triglycerides, HDL cholesterol, erythrocyte and plasma glutathione peroxidase and superoxide dismutase were estimated on automated clinical chemistry analyzer. LDL cholesterol and VLDL cholesterol were calculated. Vitamins A and E were estimated using high performance liquid chromatography (HPLC). STATISTICAL ANALYSIS: Unpaired t test was used to compare means. Binary logistic regression was done to find out the association between dependent and independent variables. RESULTS: Significantly higher levels of Total Cholesterol/HDL cholesterol and LDL cholesterol/HDL cholesterol ratio and lower HDL cholesterol levels were observed in patients when compared to controls. No significant difference of plasma and erythrocyte glutathione peroxidase and superoxide dismutase activity was observed between patients and controls. Significantly lower levels of vitamin E in patients than in controls was observed (P<0.001). Serum vitamin E was inversely associated with coronary heart disease even after controlling for age and other coronary risk factors (Odds ratio 0.898, 95% CI 0.826-0.976 P=0.01). CONCLUSIONS: The results of present study suggest that deficiency of vitamin E may be an independent risk factor of CHD. This study brings out the need for long- term monitoring of vitamin E supplementation as a preventive measure for CHD in the population studied.

Lipoprotein (A): Better assessor of coronary heart disease risk in south Indian population.

In an attempt to search for risk factors which can explain the increasing prevalence of coronary heart disease (CHD) in Indian population, we conducted a case-control study to assess the association of Lipoprotein (a)(Lp(a)) with CHD. One hundred and fifty one consecutive patients with clinical and angiographic evidence of CHD and forty-nine healthy controls were drawn for the study. Triglycerides, very low density cholesterol (VLDL-C), total cholesterol (total-C)/high density cholesterol (HDL-C) ratio, low density cholesterol (LDL-C)/HDL cholesterol ratio and Lp(a) were found to be higher in patients than controls. In female sex and in those with family history of CHD, higher total and LDL cholesterol levels were observed to be associated with higher Lp(a) levels. Lp(a) levels were also found to be higher in triple vessel disease than other vessel disease patients. Significant difference in Lp(a) levels were observed between normal coronaries vs. single and triple vessel disease(P<0.05) and also between single vs. double and triple vessel disease (P<0.01).Lp(a) levels correlated positively with vessel severity(P<0.005). Lp(a) levels >25 mg/dl were associated with coronary heart disease (Odds ratio 1.98 P<0.05 95% CI 0.007-1.18). Our findings suggest a cut-off level of 25mg/dl for determination of risk of CHD. Studies from different areas involving larger sample size are needed to confirm the findings of the present study.