Reassessing the increased glycation of hemoglobin in nondiabetic chronic renal failure patients: a hypothesis on the role of lipid peroxides

BACKGROUND: Glycated hemoglobin (HbA(1C)) is considered clinically useful for assessing long-term integrated control of blood glucose in diabetes. However, an increased HbA(1C) concentration has been documented in chronic renal failure (CRF) patients without any history of diabetes. Collective evidences reveal that lipid peroxidation (MDA) can modulate protein glycation. We evaluated the relationship between glycated hemoglobin (HbA(1C)) and lipid peroxidation in non-diabetic CRF patients. METHODS: Twenty-eight nondiabetic CRF and 23 age- and sex-matched healthy subjects were enrolled for this study. Plasma urea, creatinine, lipid peroxides, fasting glucose and HbA(1C) were analyzed in both the groups. The in-vitro effect of MDA on glycation of hemoglobin was studied by incubating healthy erythrocytes with either 5 or 50 mmol/l glucose concentration. RESULTS: The percentage of HbA(1C) concentrations and plasma malondialdehyde (MDA) were significantly increased in CRF patients compared to control subjects. When the effects of uremia and blood glucose on the concentration of HbA(1C) was refuted by partial correlation analysis, MDA was found to be a significant determinant of HbA(1C) (r=0.41, p=0.04) in patients with renal failure. In-vitro incubation of RBC with glucose along with MDA was found to enhance the process of hemoglobin glycation. CONCLUSION: Our results suggest that lipid peroxidation per se can contribute to glycation of hemoglobin, warranting extra-precaution in interpreting HbA(1C) as a measure of glycemic control in CRF.     

The relationship between the antioxidant system and anaemia in haemodialysis patients

Anaemia and oxidative stress are common features of chronic kidney disease, and both are associated with an increase in morbidity and mortality. There is growing evidence, from experimental and clinical studies, that oxidative stress may be implicated in the pathogenesis of anaemia. This study investigated the relationship between total antioxidant capacity, anaemia and serum albumin levels in 127 non-diabetic patients requiring haemodialysis. Total serum antioxidant capacity levels were determined and were found to be significantly correlated with levels of haemoglobin, haematocrit, serum albumin, serum total protein, malondialdehyde (a product of lipid peroxidation), potassium, phosphorus and alanine transaminase. There was also a significant correlation between serum albumin levels and haemoglobin and haematocrit levels. In conclusion, total antioxidant capacity was found to be inversely correlated with malondialdehyde levels and positively correlated with haemoglobin and haematocrit levels in non-diabetic patients requiring haemodialysis. Patients with high serum albumin concentrations and high total antioxidant capacity may also have high (i.e. normal) levels of haemoglobin.     

Increased glutathionyl hemoglobin in diabetes mellitus and hyperlipidemia demonstrated by liquid chromatography/electrospray ionization-mass spectrometry

BACKGROUND: Erythrocytes contain a large amount of glutathione (GSH), which protects cells from oxidative injury. The purpose of this study was to examine whether hemoglobin (Hb) is modified with glutathione by oxidation of the thiol groups in diabetes mellitus and hyperlipidemia, and to determine the oxygen affinity of glutathionyl Hb. METHODS: Hb samples obtained from patients with type 2 diabetes, patients with hyperlipidemia, and healthy subjects were analyzed by liquid chromatography/electrospray ionization-mass spectrometry (LC/ESI-MS). Glutathionyl Hb was synthesized in vitro by incubating Hb with GSH. The oxygen affinity of glutathionyl Hb was determined by measuring its oxygen dissociation curve. RESULTS: We first demonstrated that the concentration of glutathionyl Hbbeta chains is markedly increased in the diabetic patients and hyperlipidemic patients compared with healthy subjects. The in vitro synthesis of glutathionyl Hb by incubation of Hb with GSH was enhanced by adding H(2)O(2), a reactive oxygen species, into the incubation solution. The glutathionyl Hb prepared in vitro by incubating Hb with GSH showed a marked increase in oxygen affinity and a marked decrease in the Hill coefficient compared with Hb incubated without GSH. CONCLUSIONS: Glutathionyl Hb may be useful as a clinical marker of oxidative stress. The increased concentrations of glutathionyl Hb with high oxygen affinity and low cooperativity in diabetes and hyperlipidemia may lead to reduced tissue oxygen delivery.     

Hemolysis causes a decrease in HbA1c level but not in glycated albumin or 1,5-anhydroglucitol level

HbA1c has been widely used as a glycemic control indicator or as a diagnostic indicator for diabetes mellitus. However, HbA1c is affected by the erythrocyte life span and, therefore, shows falsely low values in hemolytic patients. Erythrocyte creatine (EC) is a sensitive hemolytic marker that reflects the mean erythrocyte age. In the present study, the relationships of HbA1c, glycated albumin (GA), and 1,5-anhydroglucitol (1,5-AG) with different hemolytic markers, including EC, were investigated in non-diabetic individuals. A total of 43 non-diabetic individuals whose complete blood count and reticulocytes were measured via medical examinations were included in this study (28 individuals with hemolysis and 15 individuals without hemolysis). Those with suspected diabetes mellitus based on medical history, low 1,5-AG values, or had comorbid liver and renal diseases were excluded from this study. HbA1c, GA, 1,5-AG, and various hemolytic markers were measured to examine the correlation of the glycemic control indicators with the various hemolytic markers. A significant correlation was observed between GA and 1,5-AG but not between HbA1c and GA or 1,5-AG. Significant correlations were observed between HbA1c values and various hemolytic markers (reticulocytes, haptoglobin, and EC) but not between GA or 1,5-AG values and those hemolytic markers. HbA1c, but not with GA and 1,5-AG, showed significant correlations with the hemolytic markers. These results suggested that HbA1c does not reflect the glycemic control accurately in hemolytic patients, while GA and 1,5-AG values are not affected by mean erythrocyte age and, therefore, accurately reflect the glycemic control.     

Susceptibility of erythrocyte lipids to oxidation and erythrocyte antioxidant status in myocardial infarction

Objective: We evaluated the erythrocyte lipid susceptibility to oxidation and erythrocyte antioxidant status in patients with myocardial infarction (MI).

Design and methods: Patients with MI were divided into two group according to the severity of the disease as severe (n = 30) or milder (n = 25). Malondialdehyde as a marker of lipid peroxidation was measured to show the lipid susceptibility to oxidation. Erythrocytes were stressed in vitro by hydrogen peroxide acting as the oxidative agents for 120 min. After designated time, erythrocyte MDA production was significantly higher in patients with severe MI than in controls and in patients with milder MI (p< 0.001, p< 0.001, respectively). Antioxidant status was determined by measuring the reduced glutathione levels and glutathione peroxidase activity of erythrocyte.

Results: In patients with MI, antioxidant status was significantly lower than in controls, and there was no significant difference between the patient groups.

Conclusion: Determination of erythrocyte lipid susceptibility to oxidation may be a useful in vitro test to evaluate the degree of oxidative stress in myocardial infarction.     

Comparison of oxidative damage in Malaysian end-stage renal disease patients with or without non-insulin-dependent diabetes mellitus

BACKGROUND: Comparisons of oxidative indices and total antioxidant status between end-stage renal disease (ESRD) patients with or without diabetes is scant, especially in the Asian population. METHOD: The assays were carried out according to known established protocols. RESULT: The present study showed that ESRD patients with or without non-insulin-dependent diabetes mellitus (NIDDM) did not have any significant differences in antioxidant enzyme activities, advanced glycated end products (AGE), advanced oxidized protein products (AOPP) and ferric reducing ability of plasma (FRAP), indicating that hyperglycemia does not exacerbate oxidative damage in ESRD. The regulation of catalase and glutathione peroxidase is also altered in ESRD. Elevated FRAP was observed in both ESRD groups (with and without NIDDM). The dialysis process did not alter the antioxidant enzyme activities but decreased AGEs and FRAP and increased AOPP levels. CONCLUSION: Oxidative stress is present in ESRD but this is not significantly exacerbated by hyperglycemia. The contribution of components in the pathology of renal failure towards oxidative stress exceeds that of hyperglycemia.     

Modification of renal oxidative stress and lipid peroxidation in streptozotocin-induced diabetic rats treated with extracts from Gongronema latifolium leaves

BACKGROUND: Gongronema latifolium is a tropical plant traditionally used in controlling weight gain in lactating women, as well as diabetic and overall health management. In this experiment, the aqueous and ethanolic extracts were tested to evaluate their effect on renal oxidative stress and lipid peroxidation in non-diabetic and streptozotocin-induced diabetic rats. METHODS: Diabetes was induced in male Wistar rats by intraperitoneal (i.p.) injection of streptozotocin (STZ) (65 mg/kg). The rats were divided into non-diabetic (18) and STZ-induced diabetic (18) rats, and both groups subdivided according to their treatments: aqueous extract (100 mg/kg), ethanolic extract (100 mg/kg) and control (saline solution). Aqueous and ethanolic extracts were administered by gavage in 12-h cycles over a 14-day period. RESULTS: The results indicated that the ethanolic extract significantly normalized catalase (CAT) activity (p<0.01), increased glutathione peroxidase (GPx) activity (p<0.05), and reduced reactive oxygen species (ROS) concentrations (p<0.001). It also nonsignificantly normalized superoxide dismutase (SOD) activity, increased GSH/GSSG ratio and reduced malondialdehyde (MDA) concentrations in the diabetic kidney. The aqueous extract had no effect on the superoxide dismutase activity in the diabetic animals and caused a nonsignificant increase in catalase activity. CONCLUSIONS: The ethanolic extract appeared to be more effective in reducing oxidative stress, lipid peroxidation, and increasing the GSH/GSSG ratio, thus confirming the ethnopharmacological use of G. latifolium in ameliorating the oxidative stress found in diabetics and indicating promise of possible use in lessening morbidity in affected individuals.     

Erythrocyte glutathione peroxidase activity,plasma malondialdehyde and erythrocyte glutathione levels in hemodialysis and CAPD patients

OBJECTIVES: Cardiovascular disease is the major cause of mortality in patients receiving hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) due to chronic renal failure. Increased lipid peroxidation and depletion of antioxidants may contribute to increased risk of atherosclerosis. We have therefore assessed the effect of hemodialysis and CAPD on oxidant and antioxidant status. DESIGN AND METHODS: Plasma malondialdehyde (MDA), Glutathione (GSH) levels and glutathione peroxidase (Gpx) activities were determined in 20 healthy persons (control), 20 patients on HD, 16 patients on CAPD. RESULTS: MDA was elevated in posthemodialysis and CAPD patients in comparison to prehemodialysis and control groups (posthemodialysis 1.39 +/- 0.38 nmol/mL, CAPD 1.26 +/- 0.27 nmol/mL, prehemodilaysis 0.83 +/- 0.22 nmol/mL, controls 0.72 +/- 0.21 nmol/mL p < 0.0001). With respect to antioxidants, glutathione levels were significantly lower in prehemodialysis, posthemodialysis and CAPD groups than those in control group (prehemodialysis 16.82 +/- 6.73 mg/dL RBC, posthemodialysis 31.43 +/- 11.88 mg/dL RBC, CAPD 40 +/- 12.72 mg/dL RBC, controls 62.26 +/- 24.01 mg/dL RBC, p < 0.0001). While erythrocyte GSH levels were significantly lower in the prehemodialysis patients than those in posthemodialysis and CAPD patients (p < 0.0001), it was significantly lower in posthemodialysis patients than those in CAPD patients (p < 0.05). There were no significant differences with respect to erythrocyte Gpx levels among the groups (p > 0.05). CONCLUSIONS: These findings indicate oxidative stress in patients with chronic renal failure which is further exacerbated by hemodialysis and CAPD, as evidenced by increased lipid peroxidation and low antioxidant levels.     

Glutathione in blood of patients with Friedreich's ataxia

BACKGROUND: Oxidative stress and mitochondrial dysfunction have long been considered to play a role in Friedreich's ataxia, a neurodegenerative disease due to a GAA expansion in a gene coding for a mitochondrial protein (frataxin), implicated in the regulation of iron metabolism. Since glutathione is an important antioxidant whose role has been recently proposed in the pathogenesis of some neurodegenerative diseases, we investigated glutathione metabolism in the blood of 14 patients with Friedreich's ataxia by measuring total, free and protein-bound glutathione concentrations. MATERIALS AND METHODS: Blood samples were obtained from 14 unrelated patients with Friedreich's ataxia (nine males, five females) and 20 age-matched healthy controls (10 males, 10 females). Total and free glutathione concentrations were determined by reverse-phase liquid chromatography with fluorescence detection; the glutathionyl-haemoglobin separation from healthy and pathological subjects was obtained by electrospray ionization-mass spectrometry. RESULTS: We consistently found a reduction of free glutathione levels (0.55 +/- 0.06 nmol mg(-1) haemoglobin, vs. 8.4 +/- 1.79 nmol mg(-1) haemoglobin, P < 0.001) in the blood of patients with Friedreich's ataxia, a total glutathione concentration comparable to the controls (15 +/- 2.6 nmol mg(-1) haemoglobin, vs. 15.4 +/- 1.4 nmol mg(-1) haemoglobin), and a significant increase of glutathione bound to haemoglobin (15 +/- 1.5 vs. 8 +/- 1.8%, P < 0.05) in erythrocytes. CONCLUSIONS: Our findings give evidence of an impairment in vivo of glutathione homeostasis in Friedreich's ataxia, suggesting a relevant role of free radical cytotoxicity in the pathophysiology of the disease; this study may also prove useful in the search for an oxidative stress marker in neurodegeneration.     

Application of gas chromatography-mass spectrometry for analysis of isoprostanes: their role in cardiovascular disease.

Cardiovascular disease (CVD) is the major cause of death in the Western hemisphere. Oxidative stress is involved in the pathophysiology of cancer, neurodegenerative conditions and CVD. Lipid peroxidation is one of the oxidative modifications possible in biological systems. The isoprostanes are derivatives of one specific lipid, i.e., arachidonic acid, after lipid peroxidation. Several isoprostanes have been identified in biological tissues and fluids, among them 8-iso prostaglandin F2alpha (8-iso-PGF2alpha, 8-epi-PGF2alpha, iPF2alpha-III, 15-F2t-IsoP) and its metabolite, 2,3-dinor-4,5-dihydro-8-iso-PGF2alpha. The isoprostanes are reliable in vivo markers of lipid peroxidation in humans: they are endogenously formed, characteristic in structure, ubiquitous in nature, stable in- and ex vivo and reliably quantitatable. In this Review, different analytical approaches will be discussed including immunologic, chromatographic and spectrometric techniques with the main emphasis on mass spectrometry. Analysis of isoprostanes applying radio immunoassay (RIA), enzyme immunoassay (EIA), high performance-liquid chromatography (HPLC), liquid chromatography-tandem mass spectrometry (LC-tandem MS), gas chromatography-mass spectrometry (GC-MS) and GC-tandem MS will be exemplified in the field of cardiovascular research. Results from several clinical studies are included indicating the validity of isoprostanes as surrogate parameters of oxidative stress in cardiovascular disease.     

Urinary hydrogen peroxide: a probable marker of oxidative stress in malignancy

BACKGROUND: Urinary hydrogen peroxide was postulated to be a biomarker of oxidative stress. We estimated urinary hydrogen peroxide along with other established parameters of oxidative stress in malignancies where oxidative stress is well documented. METHODS: The oxidative stress markers tested were concentrations of erythrocyte glutathione, erythrocyte malonaldehyde (MDA) and plasma hydroperoxide, and activities of plasma glutathione-S-transferase (GST) and erythrocyte catalase. Urinary hydrogen peroxide was measured by a modified ferrous ion oxidation xylenol orange version-2 (FOX-2) method on a spot random sample of urine. RESULTS: In healthy controls (n=10), erythrocyte glutathione concentration was 4.41+/-0.057mg/g of hemoglobin, plasma hydroperoxide was 2.5+/-0.07 micromol/l, erythrocyte MDA was 0.9+/-0.15 nmol/ml of packed cell suspension and erythrocyte catalase and plasma GST were 74.66+/-9.2/s/ml of packed cell suspension and 6.12+/-0.84 IU/l, respectively. In cancer patients (n=25), erythrocyte glutathione, plasma hydroperoxide and erythrocyte MDA were 9.32+/-0.42 mg/g of hemoglobin, 6.2+/-0.13 micromol/l and 2.3+/-0.27 nmol/ml of packed cell suspension, respectively; and activities of erythrocyte catalase and plasma GST were 151.04+/-6.5/s/ml of packed cell suspension and 10.9+/-0.36 IU/l, respectively. Urinary hydrogen peroxide concentration was 15+/-9.8 micromol/l in the healthy controls and 56.3+/-3.9 micromol/l in cancer patients. CONCLUSION: Urinary hydrogen peroxide may be a marker of oxidative stress in malignancies.     

An examination of the role of vitamin E in glucose-6-phosphate dehydrogenase deficiency

The effect of vitamin E on erythrocyte glutathione stability was studied both in vitro and in vivo on subjects with glucose-6-phosphate dehydrogenase deficiency. The results suggest that lipid membrane peroxidation in glucose-6-phosphate dehydrogenase deficient erythrocytes, which has been postulated to occur under conditions of oxidative stress, does not result in significant depletion of erythrocyte reduced glutathione pools. Vitamin E supplementation in these individuals was shown to have little or no effect on the response of their erythrocytes to oxidative stress.     

Lipid peroxidation in hemodialysis patients: effect of vitamin C supplementation

OBJECTIVES: Renal failure is associated with several metabolic disturbances and increasing evidences support a role of oxidative stress and impaired antioxidant defence in the pathologic mechanisms that may contribute to accelerated atherogenesis in these patients. Aim of the study was to further investigate the relationship between oxidative stress and chronic renal failure. DESIGN AND METHODS: We compared the paraoxonase (PON1) activity, the levels of lipid hydroperoxides and AGE adducts in plasma of hemodialysis patients before and after intravenous administration of vitamin C. RESULTS: An increase in lipid hydroperoxides, AGE adducts and a decrease in the activity of PON1 were observed in patients with respect to controls. The comparison before and after supplementation with vitamin C showed an increase of PON1 activity and a decrease of AGE and lipid hydroperoxides levels. CONCLUSIONS: The results provide further evidence that lipid peroxidation and impairment of antioxidant system in plasma of patients may play a role in renal disease and suggest that evaluation of PON1 activity could represents an useful approach to monitor antioxidant treatment and new dialysis therapies.     

Trimester-specific reference intervals for haemoglobin A1c (HbA1c) in pregnancy

Abstract Background: Diabetes in pregnancy imposes additional risks to both mother and infant. These increased risks are considered to be primarily related to glycaemic control which is monitored by means of glycated haemoglobin (HbA1c). The correlation of HbA1c with clinical outcomes emphasises the need to measure HbA1c accurately, precisely and for correct interpretation, comparison to appropriately defined reference intervals. Since July 2010, the HbA1c assay in Irish laboratories is fully metrologically traceable to the IFCC standard. The objective was to establish trimester-specific reference intervals in pregnancy for IFCC standardised HbA1c in non-diabetic Caucasian women. Methods: The authors recruited 311 non-diabetic Caucasian pregnant (n=246) and non-pregnant women (n=65). A selective screening based on risk factors for gestational diabetes was employed. All subjects had a random plasma glucose <7.7 mmol/L and normal haemoglobin level. Pregnancy trimester was defined as trimester 1 (T1, n=40) up to 12 weeks +6 days, trimester 2 (T2, n=106) 13-27 weeks +6 days, trimester 3 (T3, n=100) >28 weeks to term. Results: The normal HbA1c reference interval for Caucasian non-pregnant women was 29-37 mmol/mol (Diabetes Control and Complications Trial; DCCT: 4.8%-5.5%), T1: 24-36 mmol/mol (DCCT: 4.3%-5.4%), T2: 25-35 mmol/mol (DCCT: 4.4%-5.4%) and T3: 28-39 mmol/mol (DCCT: 4.7%-5.7%). HbA1c was significantly decreased in trimesters 1 and 2 compared to non-pregnant women. Conclusions: HbA1c trimester-specific reference intervals are required to better inform the management of pregnancies complicated by diabetes.     

Overexpression of erythrocyte glutathione S-transferase in uremia and dialysis.

BACKGROUND: Overexpression of glutathione S-transferase (GST; EC 2.5. 1.18) has been documented in the erythrocytes of patients with chronic renal failure, and this event may well be of relevance from a clinical standpoint. In fact, it could serve as a marker of uremic toxicity overall, which can contribute to impair the function and survival of the erythrocytes. However, the biochemical details of this phenomenon are poorly understood. METHODS: In this study, we characterized the expression of GST in erythrocytes of 118 uremic patients under different clinical conditions. The mechanisms responsible for the regulation of protein expression and enzyme activity were investigated in light of different dialysis approaches, oxidative stress, uremic toxins, erythrocyte age, and erythropoietin (EPO) supplementation. RESULTS: Mean GST activity in uremic patients was highly overexpressed with respect to controls, and this phenomenon was exclusively attributable to an increased expression of GST. Overexpression of GST did not appear to be dependent on oxidative stress and was not influenced by vitamin E supplementation. In the same manner, both erythrocyte age and EPO supplementation apparently did not interfere with the GST concentrations, which were the same in controls and patients. Preliminary experiments suggested that high-molecular weight or protein-bound toxins could play some role in the overexpression of GST. CONCLUSIONS: GST expression may be a useful marker for the individual accumulation of uremic toxins as well as of the efficiency of new dialysis strategies in removing them.     

Age-related differences in renal function at onset of renal replacement therapy in chronic kidney disease stage 5 patients

BACKGROUND: Guidelines for initiating renal replacement therapy (RRT) are based on renal function and not age, so renal function at onset of RRT is expected to be similar across age groups. AIM: To evaluate renal function at initiation of RRT across age groups. DESIGN: Observational cross-sectional study. METHODS: We extracted data for all incident chronic kidney disease (CKD) stage 5 patients (n = 322 064) commenced on chronic dialysis (haemodialysis and peritoneal) and renal transplant in the US from 1995 to 1999 from the US Renal Data Systems (USRDS). Subjects (n = 662) with incomplete data were excluded. The reminder (n = 321 402) were classified into five age groups: 0-19 years; 20-44 years; 45-64 years; 65-74 years; >/=75 years. Mean values of serum creatinine (Cr, mg/dl), creatinine clearance (CrCl, ml/min), body weight (kg) and body mass index (BMI, kg/m(2)) at onset of RRT were computed. Mean daily urinary creatinine excretion per kg body weight (CrCl x Cr/0.07/weight) was also calculated. RESULTS: Progressively lower serum creatinine levels were found in adult patients with increasing age (10.70, 8.56, 7.38 and 6.88 mg/dl in those aged 20-44 years, 45-64 years, 65-74 years, >/=75 years, respectively). CrCl was also lower in the same groups (14.76, 13.38, 11.63 and 11.60 ml/min, respectively). DISCUSSION: Older patients have a greater reduction in renal function than younger patients at onset of RRT, suggesting a delay in initiation of therapy.     

Effect of hemodialysis on the oxidative stress and antioxidants.

Oxidative stress plays a role in many disease states. These diseases have an increased incidence in uremia, and particularly in hemodialysis (HD) patients. This suggests an increased exposure to oxidative stress. An imbalance between oxidants and antioxidants has been suggested in uremic patients on HD. However, the respective influence of uremia and dialysis procedure has not been evaluated. It is postulated that antioxidant capacity in uremic patients is reduced, yet the mechanism remains unclear. We have determined the levels of lipid peroxidation expressed as thiobarbituric acid-reactive substances. We assessed oxidative protein damage by carbonyl content and activities of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in predialysis uremic patients and in end-stage renal disease (ESRD) patients before and after hemodialysis. Vitamin E and vitamin C levels, reduced glutathione and sulfhydryl content were also studied. We found enhanced oxidative stress in ESRD patients undergoing HD and in predialysis uremic patients. This was mostly due to defective antioxidant enzyme levels. Preventive modalities, including use of biocompatible membranes, ultrapure dialysate, exogenous supplementation of antioxidant vitamins, extracorporeal removal of reactive oxygen species (ROS) and oxidatively modified substances, would appear highly desirable to reduce complications in the long-term dialysis patients.     

Anaemia is common and predicts mortality in diabetic nephropathy

BACKGROUND: Diabetes is the single largest cause of chronic renal failure, accounting for 18% of patients on renal replacement therapy in the UK. AIM: To investigate the chronic kidney disease stage at which patients with diabetic nephropathy are referred to renal services, determine the prevalence of anaemia in patients with diabetic nephropathy, examine patient outcome and identity prognostic factors. DESIGN: Retrospective review. METHODS: Patients with diabetic nephropathy referred to our renal services between 1989 and 2004 were identified from electronic records. Estimated glomerular filtration rate (calculated using the MDRD formula) and haemoglobin at referral were collected. Times to renal replacement therapy and death were noted. RESULTS: We identified 508 patients. At referral, mean eGFR was 34 ml/min/1.73 m(2) and 48% of patients were at CKD stages 4 and 5. Mean haemoglobin was 11.7 g/dl; 21% had a haemoglobin <10 g/dl at referral. Median survival was 37.9 months (95%CI 33.2-42.6); median survival independent of renal replacement therapy (RRT) was 21 months (95%CI 17.8-24.6). Of patients starting RRT, 38% did so within 1 year of referral. Older age (RR 1.02, 95%CI 1.01-1.04) and lower haemoglobin (RR 0.9, 95%CI 0.85-0.99) at referral predicted death on multivariate analysis. DISCUSSION: At referral to renal services, almost 50% of patients with diabetic nephropathy were at CKD stages 4 and 5. Anaemia was common and predicted mortality. All diabetic patients from CKD stage 3 should be screened for anaemia. We believe that patients with diabetic nephropathy should be discussed with renal services when they reach CKD stage 3 with evidence of progression of renal disease.     

Beneficial effects of water-based exercise in patients with chronic kidney disease

The possible beneficial effect of regular aquatic exercise on cardiorespiratory, renal lipid parameters and oxidative stress status was studied in patients with mild to moderate renal failure. The exercise group did low-intensity aerobic exercise in the pool during a period of 12 weeks, twice a week, with sessions lasting for 30 min. Matched control participants remained sedentary. The results showed that in the exercise group all cardiorespiratory functional parameters improved and resting blood pressure lowered significantly. Proteinuria and cystatin-C were diminished significantly and glomerular filtration rate was enhanced. To evaluate the changes in oxidative stress status in the serum, products of lipid peroxidation (LPO) and serum glutathione values were measured. LPO was reduced significantly and reduced glutathione levels showed significant improvement after the exercise-conditioning programme. In the control group the data either remained the same or worsened in the same period of time. In conclusion, regular water-based exercise has beneficial effects on the cardiorespiratory, renal functional parameters and oxidative stress status in patients with moderate renal failure, and can be used in the complex rehabilitation of chronic renal failure patients, together with blood pressure control, dietary consultation, encouragement and education to prevent physical worsening and to postpone cardiovascular and renal atherosclerotic complications.     

Elevated lipid peroxidation biomarkers and low antioxidant status in atherosclerotic patients with increased carotid or iliofemoral intima media thickness.

OBJECTIVES: Lipid peroxidation plays an important role in the development of atherosclerosis, a chronic, age-related disease process of the arterial wall with onset decades prior to its clinical manifestations. The aim of the study was to assess the association between the intima media thickness (IMT) of the major arteries as a clinical marker of atherosclerosis and markers of lipid peroxidation along with the antioxidant status in humans. DESIGN: Case-control study. SETTING: A university-affiliated outpatient clinic. SUBJECTS: Thirty patients (22 males, 8 females; 70.4 +/- 7.3 years) with atherosclerosis of the carotid or iliofemoral arteries and 62 healthy controls (30 males, 32 females; 68.3 +/- 4.3 years). METHODS: Plasma levels of 8,12-isoprostane F2alpha-VI (8,12-IPF2alpha-VI) were measured by gas chromatography/mass spectrometry, whereas levels of malondialdehyde (MDA), vitamins A (retinol) and E (alpha- and gamma-tocopherol), and carotenoids were determined by high-performance liquid chromatography. The IMT was measured by B-mode ultrasonography. RESULTS: Patients showed, independent of fruit and vegetable intake, significantly lower plasma levels of retinol, alpha-tocopherol, and all carotenoids excluding beta-cryptoxanthin compared with controls. On the contrary, plasma 8,12-IPF2alpha-VI levels were almost doubled (p < .001) and MDA levels increased by one-third (p < .01) in atherosclerotic patients compared with controls. CONCLUSIONS: The analyses of isoprostanes and antioxidant nutrients in plasma as markers of oxidative stress and the parallel evaluation of IMT as a structural marker of atherosclerosis are suitable tools for investigating the role of antioxidants and oxidative stress in atherosclerosis.