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Background: Glycated hemoglobin A1c (HbA1c) among diabetic hemodialysis patients continues to be the standard of care, although its limitations are well recognized. This study evaluated glycated albumin (GA) and glycated serum protein (GSP) as alternatives to HbA1c in detecting glycemic control among diabetic hemodialysis patients using continuous-glucose-monitoring (CGM)-derived glucose as reference standard. Methods: A CGM system (iPRO) was applied for 7 days in 37 diabetic hemodialysis patients to determine glycemic control. The accuracy of GA and GSP versus HbA1c in detecting a 7-day average glucose ≥184 mg/dL was evaluated via receiver-operating-characteristic (ROC) analysis. Results: CGM-derived glucose exhibited strong correlation (r = 0.970, p < 0.001) and acceptable agreement with corresponding capillary glucose measurements obtained by the patients themselves in 1,169 time-points over the 7-day-long CGM. The area under ROC curve (AUC) for GA, GSP, and HbA1c to detect poor glycemic control was 0.976 (0.862–1.000), 0.682 (0.502–0.862), and 0.776 (0.629–0.923) respectively. GA levels >20.3% had 90.9% sensitivity and 96.1% specificity in detecting a 7-day average glucose ≥184 mg/dL. The AUC for GA was significantly higher than the AUC for GSP (difference between areas: 0.294, p < 0.001) and the AUC for HbA1c (difference between areas: 0.199, p < 0.01). Conclusion: Among diabetic hemodialysis patients, GA is a stronger indicator of poor glycemic control assessed with 7-day-long CGM when compared to GSP and HbA1c.

ObJEct IVE: t he aim of this study was to evaluate the changes in the levels of vasoactive eicosanoid hormone-like substances PGE 2, PGI2 and t XA2 in hemodialysis (HD) patients who were following a long-term physical training program during the hemodialysis session. DE sIGN: A total of 50 patients with c hronic Kidney Disease ( c KD) (stage 5) on hemodialysis and 35 healthy individuals who served as controls ( c ) were evaluated. t he 50 c KD patients were divided into two groups: the HD group consisted of 31 patients who received usual care without any physical activity during the hemodialysis sessions, while group HD/Exer included 19 patients who followed a program of physical exercise for six months. Plasma levels of PGE 2, 6-Keto-PGF1α (the stable derivative of PGI 2) and t Xb 2 (the stable derivative of t XA2) were measured by reliable enzymo-immunoassay methods (EIA) in HD and HD/Exer patients before and after the hemodialysis sessions as well as in the group of c . rEsULts : t he plasma levels of PGE 2 and 6-keto-PGF1α in group HD Exer/ before patients were higher than those in group HD before (20.39±5.82 and 1449.19±553.41 vs 17.68±5.36 and 1295.10±384.43 pg/ml, p=0.044 and p=0.067, respectively), while the plasma levels of t Xb 2 were lower in HD Exer/ before patients compared to HD before(499.76±67.51 vs 608.01±80.23 pg/ml, p=0.041). t he plasma levels of PGE2 and 6-keto-PGF1α in group HD Exer/ after patients were significantly higher compared to those in HDafter patients (23.01±5.70 and 1618.19±435.07 vs 16.57±4.97 and 1005.44±317.16 pg/ ml, p

Objective: To assess the effects of intradialytic exercise training on health-related quality of life indices in haemodialysis patients.Subjects/patients: Thirty-five patients on haemodialysis, with a mean (SD) age of 48.8 (13.9) years, volunteered to participate in the study. They were randomized either to rehabilitation group (group A: 19 patients), following a 10-month intradialytic exercise training programme or to control group (group B: 14 patients). After the randomization, two of the patients, one of each group, withdrew from the study for reasons unrelated to exercise training.Method: All patients at the beginning and the end of the study underwent clinical examination, laboratory tests and a treadmill exercise testing with spiroergometric study for the evaluation of their aerobic capacity (Vo2peak). A formal psychosocial assessment, which included affective (Beck Depression Inventory), health-related quality of life (Quality of Life Index, Living Questionnaire of Minnesota, Life Satisfaction Index and Short Form-36 questionnaire) and personality (Eysenck Personality Questionnaire) parameters, was evaluated at beginning and end of the study. The dose of erythropoietin was changed as needed, according to the level of the haemoglobin, aiming to keep it at 11 (2) g/dL during the study.Results: Baseline values were similar between the two groups. After training in group A, Vo2peakwas increased by 21.1% (PConclusion: The results demonstrated that intradialytic exercise training improves both physical functioning and psychological status in haemodialysis patients, leading to an improvement of patients' quality of life.

Background: Arterial baroreflex sensitivity (BRS) evaluation has been increasingly used as an index of cardiac autonomic control. Cardiac autonomic dysfunction leading to depressed BRS has been associated with an increased risk of ventricular arrhythmias and sudden death in patients with chronic kidney disease (CKD) on hemodialysis (HD). Aim: The purpose of this study was to investigate the effects of an exercise training program during hemodialysis on BRS in CKD patients. Patients and methods: 43 HD patients participated in the study. They were randomly assigned into either a 7-month exercise training program during HD (Group A: n = 22 patients) or a sedentary control group (Group B: n = 21 patients). Additionally, 20 sex- and age-matched sedentary individuals comprised a healthy control group (Group C). All patients at the beginning and the end of the study underwent a tilt test for evaluation of BRS and an exercise testing with spiro-ergometric study for cardiorespiratory capacity estimation. The level of Hb, medications and the HD procedure remained stable during the study. Results: At baseline BRS was found to be reduced by 51.5% (p < 0.05) and baroreflex effectiveness index (BEI) by 36.4% (p < 0.05) in Group A compared with Group C. Initially, all HD patients had also significantly lower exercise time and VO 2 peak than the healthy subjects. After training, Group A showed a significant improvement in BRS by 23.0% (p < 0.05), in BEI by 27.0% (p < 0.05), in event and ramp count by 35.0% (p < 0.05) and 29.0% (p < 0.05), respectively as well as in VO 2 peak by 22.4% (p < 0.05) and in exercise time by 40.9% (p < 0.05). Significant correlations were found between BRS and METS (r = 0.476, p < 0.05), BRS and VO 2 peak (r = 0.443, p < 0.05), BEI and METs (r = 0.492, p < 0.05), BEI and VO 2 peak (r = 0.467, p < 0.05), event count and VO 2 peak (r=0.715,p

Background/Aims: Increased oxidative stress in chronic kidney disease (CKD) was suggested to be both a cause and an effect of renal injury. However, the evolution of oxidant stress from early stages of renal function decline is not fully clear. This study aimed to determine the oxidant-antioxidant balance across the whole range of renal function. Methods: A total of 116 patients with CKD (85 predialysis patients divided into groups according to CKD stage, and 31 patients with end-stage renal disease (ESRD) on hemodialysis treatment), as well as 29 healthy subjects were evaluated. Plasma levels of 15-F2t-isoprostane (15-F2t-IsoP), a valid marker of oxidant stress, as well as total antioxidant capacity (TAC) and serum levels of vitamin E were measured in all participants. Results: Plasma 15-F2t-IsoP levels were higher in predialysis and ESRD patients compared to healthy subjects and were progressively increasing with advancing CKD stages (p < 0.001). In contrast, plasma TAC was similar between healthy subjects and predialysis patients, and presented a small reduction in ESRD patients (p < 0.001). Vitamin E levels were higher in healthy subjects compared to any other group (p < 0.001) and slightly higher in ESRD patients compared to predialysis patients (p < 0.01), but did not differ significantly between the groups of predialysis patients. Plasma 15-F2t-IsoP levels were inversely correlated with estimated glomerular filtration rate in predialysis patients (r = –0.65, p < 0.001). Conclusions: This study shows that 15-F2t-IsoP levels increase progressively with advancing CKD stages, whereas TAC and vitamin E levels remain rather stable with the loss of renal function and change only in patients with ESRD.

Digital clubbing due to secondary hyperparathyroidism has been described as an unusual complication among patients with chronic kidney disease undergoing maintenance hemodialysis therapy. Although the pathogenesis of digital clubbing is unknown, certain growth factors such as platelet-derived growth factor and hepatocyte growth factor have been associated with this clinical syndrome. Two patients of our renal unit population presented this unique clinical feature bilaterally, among the other clinical findings of severe secondary hyperparathyroidism. Both patients were subjected to parathyroidectomy. Histological examination revealed diffuse hyperplasia of parathyroid glands. Despite the improvement of clinical symptoms and laboratory findings of secondary hyperparathyroism after parathyroidectomy, digital clubbing remained unchanged.

Background: Atherosclerotic cardiovascular events are a major cause of morbidity and the main cause of mortality in hemodialysis patients. Hyperhomocysteinemia – which is a consistent finding in uremic patients – is considered an independent risk factor for cardiovascular disease (CVD). However, the relationship between plasma homocysteine (Hcy) concentrations and atherosclerotic CVD has not been extensively investigated. Patients and Methods: 37 patients undergoing chronic hemodialysis and 30 healthy individuals (control group), sex- and age-matched, were included in this study. Both healthy controls and hemodialysis patients underwent echo-Doppler carotid artery examination. The right and left carotid arteries were assessed separately. Our observation included measurements of the ultrasound images of the intimal wall thickness, the lumen diameter and the atherosclerotic plaques. We determined plasma Hcy, vitamin B12 and folic acid levels and serum cholesterol, triglycerides, HDL, ApoA-I, ApoB-100, Lp(a), CRP, albumin and creatinine levels in blood samples from both studied groups. We also determined the urea reduction ratio in the patient groups. The epidemiological as well as the biochemical data were correlated with the findings of the carotid artery examination. Results: Plasma Hcy levels were significantly increased in hemodialysis patients compared to controls (33 ± 12.3 vs. 12.27 ± 7.47 µmol/l, p < 0.001). Intimal wall thickness, lumen diameter and number of atherosclerotic plaques of both carotid arteries were significantly higher (p < 0.01 or p < 0.001) in patients compared to controls. There was a significant positive correlation between plasma Hcy levels and the number of the atherosclerotic plaques (r = 0.41, p < 0.01 in the right and r = 0.49, p < 0.001 in the left carotid artery). Lumen diameter was significantly (p < 0.01) associated with age, MAP and CRP levels. Significant correlations (p = 0.05–0.01) were also found between the number of the plaques and age as well as the duration of hemodialysis, while folic acid levels were inversely correlated with the number of the plaques. Conclusions: Both hyperhomocysteinemia and atherosclerotic indices of the carotid arteries are more prevalent in hemodialysis patients compared to healthy controls. Elevated plasma Hcy levels were associated with the carotid artery atherosclerotic indices in chronic hemodialysis patients.

OBJECTIVE: The concentration of 8-iso-prostaglandin-F2α (8-iso-PGF2α) in biological fluids has been considered as the most reliable biochemical index of the lipid peroxidation and oxidative stress in patients with several pathological conditions including end stage renal failure. However, there is no reference regarding the influence of hemodialysis (HD) on the values of 8-iso-PGF2α in the muscle Interstitial Fluid (IF) of patients with end stage renal failure. The aim of our study was to determine 8-iso-PGF2α concentration in the IF during hemodialysis and the gradient between plasma and IF in patients with end stage renal failure. DESIGN: In this study, two microdialysis probes were inserted into the vastus lateralis muscle of the right leg of six male patients with end stage renal failure who were on hemodialysis, and in six healthy males (controls). The samples of IF (12 dialysate fluids) were collected after an equilibration of 30 min: a) during the 1st hour preceding hemodialysis (group CRF0), b) during the 1st, 2nd, 3rd and 4th hour while on hemodialysis (groups CRF1, CRF8, CRF3 and CRF4) and c) during the 1st hour following hemodialysis (group CRF5). At the end of the above periods and simultaneously, blood samples were drawn from the arteriovenous fistula. In the controls, the IF samples (twelve dialysate fluids) were collected during a period of one hour and the blood samples at the end of this period. The levels of 8-iso-PGF2α were measured with an enzyme-immunoassay method. Statistical evaluation was carried out with the statistical program NCSS 2000 and the ANOVA test. RESULTS: Plasma and IF levels of 8-iso-PGF2α in the patients were significantly higher than in controls at base line. During hemodialysis, the 8-iso-PGF2α rose progressively both in plasma and IF but remained higher in plasma than in IF. CONCLUSIONS: Lipid peroxidation is higher in patients on hemodialysis than in controls but it is lower in the IF compared to plasma. The mechanism for this gradient is speculative.

Within the past years, several epidemiologic studies have shown that insulin resistance and hyperinsulinemia are associated with chronic kidney disease, and experimental data suggest that a number of background mechanisms could connect insulin resistance with renal injury. Moreover, the acute sodium-retaining action of insulin at the kidney level has been proposed to participate in the development of salt sensitivity in essential hypertension. Current knowledge suggests that oxidative stress can be involved in the development of renal injury and can also promote primary salt retention at the kidney level. Insulin resistance and hyperinsulinemia seem to be closely connected with oxidative stress in the form of a vicious circle. This article discusses the potential role of oxidative stress as a mediator of the renal effects of insulin resistance/hyperinsulinemia.

There are a few reported cases in the literature of thrombotic thrombocytopenic purpura (TTP), associated with systemic lupus erythematosus (SLE). We describe two cases of TTP which have been presented during rapidly progressive lupus nephritis, with grand-mal seizures, thrombocytopenia and microangiopathic hemolytic anemia. Both cases were treated with hemodialysis, plasma exchange, corticosteroids, cyclophosphamide and intravenous gamma-globulin. In both cases the TTP was improved but not the renal function. Further experience is needed to determine whether intensive and prompt treatment with plasma exchange, corticosteroids and chemotherapy leads to a favorable outcome, in cases of TTP associated with SLE.

Studies in experimental models of renal ischemia have shown that calcium antagonists are effective in the protection from the ischemic insult. Thirty-five patients who received a kidney graft over a 2-year period (nifedipine group) were compared with 35 consecutive transplanted patients (control group). The two groups were compatible with regard to age, sex, duration of hemodialysis, graft matching, and total number of blood transfusions. The patients in the nifedipine group were given 0.2 mg nifedipine (10% solution) through the renal artery immediately after revascularization, and also nifedipine per os during all the study periods. Adequate diuresis (1 mL/min) was obtained in 14.5 +/- 37.2 and 43.9 +/- 46.8 h after transplantation in the nifedipine and control groups respectively (p0.01). The frequency of acute tubular dysfunction and the mean serum creatinine concentrations were found to be higher in the control group. Fractional excretion of sodium was not found to be different in the two groups on the first day, but it was significantly lower by the first week after transplantation in the nifedipine group (p0.05). Acute rejection episodes were found to be more frequent in the control group during the first 6 months after transplantation (p0.05). It is suggested that nifedipine is effective in the protection of renal function after transplantation.

Background: The most common cause of post-transplant dyslipidemia is the use of corticosteroids and cyclosporin-A (CyA). The HMG-CoA reductase inhibitors have emerged as the agents of first choice in the treatment of post-transplant hyperlipidemia in combination with low fat diet. The objective of this study was to evaluate the efficacy of combined treatment with low-dose pravastatin and fish oil in post-renal transplantation dislipidemia. Patients and Methods: Twenty-four renal transplant patients, 15 men and 9 women aged from 30 to 60 years with stable renal function were included in this study. All patients were transplanted from living related donors and were given a stable triple immunosuppressive therapy, with methylprednisolone, azathioprine and CyA. All patients were also given a standard diet containing 1 g/kg BW protein, reducing the daily fat to less than 30%, and maintaining at least a 1:1 ratio of saturated to polyunsaturated (or monounsaturated) fats. A dosage of 20 mg pravastatin (pravachol) and 1 g of fish oil (prolipid) were added to the diet after dinner, according to our protocol. Blood samples were taken after each study period for total cholesterol, LDL-cholesterol, triglycerides, Apo A1, Apo B, Lp(a), creatinine, CPK and fibrinogen determination. Results: At the end of the therapeutic protocol with pravastatin a significant reduction (p < 0.02) of total and LDL-cholesterol was observed, but no significant change in triglycerides, HDL, Lp(a), Apo A1, Apo B and fibrinogen was shown. At the end of the therapeutic protocol with pravastatin and fish oil supplement significant changes were seen in TC (p < 0.02), TG (p < 0.03), LDL-C (p < 0.03), Apo A1 (p < 0.04) and Apo B (p < 0.05) concentrations. There were no significant changes in HDL-C and Lp(a) concentrations. Renal function and cyclosporine levels were not changed during and after the study. CPK was increased only in one case. Conclusions: It is suggested that if the response to the diet is inadequate, the use of combined treatment with low-dose pravastatin and fish oil is a more effective strategy than the pravastatin treatment alone for changing the lipid profile after renal transplantation.

Lipid peroxidation is a critical pathway of reactive oxygen species inducing tissue injury in postischemic acute renal failure. In order to evaluate the effect of renal ischemia reperfusion on kidneys, renal tissue malondialdehyde (MDA, nmol/g wet weight) concentration was measured in 29 male Wistar rats subjected to a midline abdominal incision and 60 min occlusion of the left renal artery. A right nephrectomy was performed at the beginning of the ischemic period. The animals were separated in four groups. Groups 1 (n = 7) and 3 (n = 7) underwent 60 min of ischemia and 15 min of reperfusion, respectively. Groups 2 (n = 8) and 4 (n = 7) were subjected to the same procedure but, in addition, they received 2.5 mg/kg TMZ into the tail vein 2 h prior to the left renal artery occlusion. A significant elevation of MDA after 60 min of ischemia (1.43 vs. 2.1, p < 0.001), which was augmented after 15 min of reperfusion (1.4 vs. 3.72, p < 0.001) was observed. Furthermore, there was a significant reduction of renal tissue MDA in ischemic rats treated with TMZ (group 3) (2.1 vs. 1.52, p < 0.001). The maximum reduction of renal tissue MDA was observed in ischemic-reperfused rats (group 4) that had received TMZ (3.72 vs. 1.36, p < 0.001). It is suggested that lipid peroxidation is a critical event in postischemic acute renal failure, and TMZ is a useful protective agent of renal damage from oxygen free radicals.

Erythrocytosis occurs in 10-15% of renal transplant recipients and there is evidence that the production of erythropoietin is modulated by adenosine. We prospectively evaluated the effects of theophylline, a nonselective adenosine antagonist, in 8 patients with erythrocytosis after renal transplantation. All patients were given triple-drug immunosuppressive therapy with methylprednisolone (8 mg/daily), azathioprine (2 mg/kg b.w. daily) and cyclosporin A (4 mg/kg b.w. daily). After an 8-week course of theophylline treatment (Theodur 300 mg x 2 daily), the mean serum erythropoietin levels were significantly reduced (from 61 mIU/ml before to 16.5 mIU/ml after treatment, p0.05). Also the hematocrit was reduced from 0.58 before to 0.50 after treatment (p0.05). The previous requirement of monthly phlebotomy was eliminated in all transplant recipients. The above effects were reproducible when the patients were rechallenged with theophylline after a recovery period. It is suggested that theophylline modulates the production of erythropoietin as well as the hematocrit levels in patients with erythrocytosis after renal transplantation and may be useful in the treatment of this condition.

Six healthy dogs, after control measurements, were subjected to renal artery occlusion for 90 min, under general anesthesia. 5 mg of PGE2 (Prostin E2, Upjohn) diluted in 100 mL of normal saline was infused directly into the left renal artery for 90 min (PG group), while only normal saline was infused into the right renal artery (control group). After removal of the clamps blood and urine samples were collected every hour for the first 3 h of revascularization and both kidneys were then removed for histological study by light microscopy. PG kidneys regained urine flow above the oliguric levels within 3 hr of revascularization (0.30 +/- 0.04 mL/min vs 0.14 +/- 0.03 mL/min in controls (p less than 0.001). Creatinine, urea, and osmolar clearances were also significantly higher in PG group (p less than 0.01 or p less than 0.001 for 2 and 3 hr of follow-up after revascularization). Urine sodium concentration and fractional sodium excretion (FENa) (%) were not significantly lower in the PG group compared to the controls. Histology showed focal brushborder loss, hyaline and granular casts, focal tubular dilation, and focal necrotic lesions on the tubular cells in both groups of kidneys. A direct cytoprotective effect of the PGE2 was not found. It is suggested that PGE2 is effective in the protection of renal function when it is administered during the mechanical occlusion model of acute renal failure in anesthetized dogs.

Twelve patients, 8 male and 4 female, aged from 26 to 70 years were studied. They were on hemodialysis (HD) 4 h three times weekly with cuprophan hollow fiber dialyzers (Gambro 120M) and dialysate containing 35 mEq/L of acetate. The study compares two random HD sessions on each patient. Sixty minutes prior to one random session a placebo was administered orally, and prior to another random session piracetam was given at a dose of 8 g. Heparin dosage was not reduced during HD using QB 200 ml, QD 500 ml, and no ultrafiltration. Blood samples for leukocyte and platelet counts, serum C3, arterial paO2 and paCO2, thromboxane-B2 (TxB2), and β-thromboglobulin (β-TG) were taken from the arterial line before and at 15, 60, and 240 min during HD. Leu-kopenia at 15 min of HD was found to be less severe (p < 0.01) in the piracetam study than in the placebo, whereas platelet count did not change. Serum C3 was slightly increased in both studies. Arterial oxygen was preserved close to the initial levels by piracetam (91.66 mm Hg versus 81.08, p < 0.01 at 60 min, and 93.08 versus 80.17 mm Hg, p < 0.01 at 240 min of HD sessions) but paCO2 did not change significantly. TxB2 increased less with piracetam in comparison to placebo (p < 0.01 or p < 0.001), but (J-TG was reduced significantly by piracetam at any time during HD (p < 0.001). The above statistical analysis was done by paired t-test. Using the ANOVA test, significance was found only in plasma TxB2 levels between the two groups (p < 0.001). It is suggested that piracetam is a potent inhibitor of some HD-associated bioincompat-ibility parameters.