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BACKGROUND AND AIMS Continuous-glucose-monitoring (CGM) facilitates the assessment of interday glucose variability and identification of acute excursions of hyper- and hypoglycemia [1–4). METHOD Among 37 diabetic hemodialysis patients who underwent 7-day CGM with the iPRO2 device (Medtronic Diabetes, Northridge, CA, USA), we explored the accuracy of GA and hemoglobin A1c (HbA1c) in assessing glycemic control, using CGM-derived metrics as the reference standard. RESULTS In receiver-operating-characteristic (ROC) analysis, the area under the curve (AUC) in diagnosing a time in target glucose range of 70–180 mg/dL (TIR70-180) in 250 mg/dL (TAR >250) in >10% of readings did not differ from that of HbA1c [AUC 0.854 (95% CI 0.699–0.948)] (P = 0.16). GA [AUC 0.712 (95% CI 0.539–0.848)] and HbA1c [AUC 0.740 (95% CI 0.570–0.870)] had a similarly lower efficiency in detecting a time below target glucose range 1% of readings (P = 0.71). Although the mean glucose levels were similar, the coefficient of variation of glucose recordings (39.2% ± 17.3% versus 32.0% ± 7.8%, P CONCLUSION The present diagnostic test study shows that among diabetic hemodialysis patients, GA had higher accuracy than HbA1c in detecting a 7-day CGM-derived TIR70-180 in

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.

Familial microscopic hematuria (FMH) is associated with a genetically heterogeneous group of conditions including the collagen-IV nephropathies, the heritable C3/CFHR5 nephropathy and the glomerulopathy with fibronectin deposits. The clinical course varies widely, ranging from isolated benign familial hematuria to end-stage renal disease (ESRD) later in life. We investigated 24 families using next generation sequencing (NGS) for 5 genes: COL4A3, COL4A4, COL4A5, CFHR5 and FN1. In 17 families (71%), we found 15 pathogenic mutations in COL4A3/A4/A5, 9 of them novel. In 5 families patients inherited classical AS with hemizygous X-linked COL4A5 mutations. Even more patients developed later-onset Alport-related nephropathy having inherited heterozygous COL4A3/A4 mutations that cause thin basement membranes. Amongst 62 heterozygous or hemizygous patients, 8 (13%) reached ESRD, while 25% of patients with heterozygous COL4A3/A4 mutations, aged >50-years, reached ESRD. In conclusion, COL4A mutations comprise a frequent cause of FMH. Heterozygous COL4A3/A4 mutations predispose to renal function impairment, supporting that thin basement membrane nephropathy is not always benign. The molecular diagnosis is essential for differentiating the X-linked from the autosomal recessive and dominant inheritance. Finally, NGS technology is established as the gold standard for the diagnosis of FMH and associated collagen-IV glomerulopathies, frequently averting the need for invasive renal biopsies.

Background/Aims: In experimental models of polycystic kidney disease impaired bioavailability of nitric oxide (NO) and elevated mRNA expression of oxidative stress markers at the kidney level was noted. However, clinical studies investigating the potential role of endothelial dysfunction and oxidative stress in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD) are limited. We evaluated asymmetric dimethylarginine (ADMA) as marker of NO synthase inhibitor as well as 15-F2t-Isoprostane and oxidized-low density lipoprotein (oxidized-LDL) as measures of oxidative stress in patients with early stages ADPKD. Methods: We recruited 26 ADPKD patients (Group A) with modestly impaired renal function (eGFR 45-70 ml/min/1.73m2), 26 age- and sex-matched ADPKD patients (Group B) with relatively preserved renal function (eGFR)>70 ml/min/1.73m2), and 26 age- and sex-matched controls (Group C). Determination of circulating levels of ADMA, 15-F2t-Isoprostane, oxidized-LDL and routine biochemistry was performed. Results: Group A and B had significantly higher ADMA levels as compared to controls (1.68±0.7 vs 0.51±0.2 μmol/l, P2t-IsoP and oxidized-LDL levels were also significantly higher in Group B relative to controls (788.8±185.0 vs 383.1±86.0 pgr/ml, P2t-Isoprostane (r=0.811, PConclusion: This study shows elevation in circulating levels of ADMA along with aggravation of oxidative stress from the early stages of ADPKD.

Asymmetric dimethylarginine (ADMA) is a naturally occurring amino acid found in tissues and cells that circulates in plasma and is excreted in urine. It inhibits nitric oxide synthases (NOs) and produces considerable cardiovascular biological effects. Several studies have suggested that plasma concentrations of ADMA provide a marker of risk for endothelial dysfunction and cardiovascular disease. In animal and in population studies ADMA has been associated with progression of CKD. Several mechanisms may be involved in this association, such as compromise of the integrity of the glomerular filtration barrier and development of renal fibrosis. This review summarizes the existing literature on the biology and physiology of ADMA focusing on its role in the progression of renal disease.

Matrix metalloproteinases (MMPs) are zinc-dependent proteases that degrade components of the extracellular matrix (ECM). In glomerular disease, MMPs are major regulators of ECM degradation as well as structural and functional integrity in the glomerulus. In altered matrix composition diseases, glomerular damage is due to increased degradation of kidney and vessel basement membranes (BMs) by MMPs. MMP -2 and -9 are both considered as the main enzymes that degrade collagen type-IV (coll-IV), which represents the key collagenous component of ECM and constitutes the architectural structure of vessels and glomerular BM. Τhere is growing evidence implicating MMPs in atherosclerosis as well as in cardiovascular disease (CVD) and chronic kidney disease (CKD). Specific endogenous tissue inhibitors of MMPs (TIMPs) are also implicated in CKD, CVD and diabetic nephropathy (DN). The present review discusses the role of MMPs -2 and -9 in DN, as a leading cause of end-stage renal disease and as a model of the link between progressive glomerulosclerosis and MMP expression.

Noninvasive screening studies may identify hemodialysis (HD) patients at increased risk of sudden cardiac death. Interventions that improve the findings of such screening studies may reduce sudden cardiac death.Randomized and controlled clinical trial.59 HD patients were randomly assigned to an exercise training group (group A; 30 patients) or control group (group B; 29 patients).Group A participated in a 10-month supervised exercise training program during the HD sessions (3 times weekly).Each risk factor separately and the composite risk score. Patients were considered high risk according to the criteria (aerobic capacity: peak oxygen consumption [Vo(2)peak]or = 14 mL/kg/min, left ventricular ejection fractionor = 30%, SD of normal RR intervals [SDNN]or = 70 milliseconds, positive T-wave alternans, or positive late potentials). Statistical analysis included a 2-group comparison of change scores and analysis of covariance adjusting for baseline.At entry and end of the study, Vo(2)peak and left ventricular ejection fraction were estimated, heart rate variability was calculated (measurement of SDNN, mean RR intervals), and the ratio between low- (LF) to high-frequency (HF) components (LF/HF) and late potentials and T-wave alternans were detected.Baseline measurements were similar between the 2 groups. At follow-up, 9 patients from group A and 20 from group B (P = 0.003) were considered high risk. The change in number of risk markers over time was significantly different between groups (-0.5 +/- 0.7 in group A versus 0.07 +/- 0.3 in group B; P0.001). Additionally, the change in Vo(2)peak over time was 3.5 +/- 3.2 in group A and -0.2 +/- 3.5 mL/kg/min in group B (P0.001), left ventricular ejection fractions were 3.4% +/- 3.9% and 0.2% +/- 7.7% (P0.05), SDNNs were 12.6 +/- 16.3 and -1.1 +/- 10.2 milliseconds (P0.001), and LF/HF ratios were 0.3 +/- 0.4 and -0.1 +/- 0.3 (P0.001), respectively. Change in numerical score of the signal-averaged electrocardiogram also was found to be statistically different (P0.05) between groups.Clinical outcomes, including survival, were not assessed.Exercise training improves aerobic capacity and ameliorates some indicators of risk of sudden cardiac death in HD patients.

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.

In a side-to-side fistula between femoral artery and vein, an external “shunt” was created that simultaneously connected the distal femoral vein and the proximal femoral vein in 14 normal dogs with weight ranging from 14 to 28 kg. Blood flow and pressure alterations of different sites of this experimental model of vascular access were studied. The results showed that the degree of blood flow on these two vascular communications depends on the structural integrity of the femoral artery with adequate blood flow and blood pressure. Also, the correct connection of external shunt with the fistula is of equal importance. It is suggested that the blood pressure as well as the blood flow rate of these two vascular communications were adequate to allow performance of acute and chronic hemodialysis.

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.

Reports on the association of multiple myeloma with systemic vasculitis are rare and concern, vasculitis due to crystalglobulin deposition in vessels or to polyarteritis nodosa PAN-like type necrotizing vasculitis. The association of multiple myeloma with MPO-ANCA positive microscopic polyangiitis has not yet been described. We report a case of a 72 year old man, who was referred to our clinic for evaluation of recent onset renal failure (serum creatinine 8mg/dl), proteinuria 2g/day, severe anemia (hematocrit 16%) and fever accompanied by malaise, anorexia, weigh loss, myalgia and arthralgia. These symptoms appeared 20 days prior to his admission. There was no evidence of any infection. The renal biopsy showed necrotizing crescentic glomerulonephritis. The MPO-ANCA were positive. Bone marrow biopsy revealed infiltration with IgG-lambda neoplastic plasma cells. The patient was treated with hemodialysis, plasma exchange, corticosteroids and cyclophosphamide. Even though his clinical situation and renal function improved gradually, two months after his admission, he developed acute respiratory insufficiency accompanied by heavy hemoptysis, patchy infiltration on chest X-rays, due to lung vasculitis and died. Multiple myeloma should be considered in the differential diagnosis of hematological neoplasms capable of causing paraneoplastic ANCA positive microscopic polyangiitis.

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.

8-Iso-prostaglandin F2alpha (8-iso-PGF2alpha) is a characteristic F2-isoprostane which is produced in humans via a free radical-catalysed lipid peroxidation mechanism of arachidonic acid, independent of the cycloxygenase pathway. The measurement of the plasma levels of 8-iso-PGF2alpha was shown to be the most reliable biochemical index of oxidant stress status in the human body. However, there is no reference in literature of local muscle interstitial 8-iso-PGF2alpha production during dynamic muscle contractions. The aim of the present study was to evaluate the response of 8-iso-PGF2alpha during intensive exercise with a cycle ergometer. Two microdialysis probes with CMA-60 microdialysis catheters were inserted into the vastus lateralis muscle of the right leg of six healthy male volunteers. After insertion, these microdialysis probes were attached to a perfusion pump that perfused ringer acetate solution at a rate of 0.3 microl/min. The dialysate fluid samples were collected: (a) during a 30 min rest period and (b) during a 30 min period of dynamic exercise with a cycle ergometer at 150 Watts. Our measurements showed that the levels of 8-iso-PGF2alpha in the interstitial fluid (IF) of the vastus lateralis muscle increase significantly during exercise (from 113.5 +/- 30.2 to 329.9 +/- 69.8 pg/ml, P = 0.05). In conclusion, dynamic muscle exercise produces a local increase of the IF levels of 8-iso-PGF2alpha due to local peroxidation injury of the contractive muscle. The microdialysis method is widely applied, easily repeated and it could contribute in evaluating the local lipid muscle peroxidation during intensive exercise.

Background/Aims This study aimed to evaluate the safety and efficacy of the ProCol, vascular bioprostheses as vascular access (VA) material, especially in patients with a history of prior failed access. Methods During a 20-month period, 25 arteriovenous (AV) bovine vein grafts were placed in 24 hemodialysis (HD) patients for VA. All patients presented with failed autologous access sites. Results Graft placement was successful in all patients with no procedure-related complications. Follow-up from 6–26 months gave primary 6-month, 12-month and 24-month patency rates of, respectively, 90%, 80% and 70%. Graft characteristics in cannulation and hemostasis were very satisfying. Conclusion Our midterm results demonstrated that the ProCol, vascular bioprosthesis was a promising material for VA with good patency and low complication rates.

The aim of the present study was: (a) to assess the effect of HBsAg on the survival of both renal grafts and patients, and (b) to determine the outcome of HBV chronic infection after renal transplantation. Fourteen patients seropositive for HBsAg but asymptomatic before renal transplantation (group A) were included in the study. The results were compared to those of 14 transplanted patients (group B) seronegative for HBsAg with similar age and immunosuppressive treatment. Four patients received a graft from a living-related donor and 10 patients from a cadaver donor in each group. Eight of 14 patients of group A showed, after renal transplantation, chronic hepatitis, which was not observed in any of the group B patients (p < 0.01). The rate of acute rejection episodes was significantly greater (p < 0.05) in group B than in group A. The graft survival was found to be similar in both groups at the 1st year, but significantly less (p < 0.01) in group B than in group A at the 5th year after transplantation. The survival of patients was found to be significantly less in group A than in group B at the 1st (p < 0.05) and 5th years (p < 0.01) after transplantation. In 2 patients of group A and 1 of group B anti-HCV was found, while HDAg plus anti-HD was found in 1 patient of group B. The HBV-DNA was found in 4 of 8 alive patients of group A.(ABSTRACT TRUNCATED AT 250 WORDS)

Asymmetric dimethylarginine (ADMA) is a naturally occurring amino acid found in tissues and cells that circulates in plasma and is excreted in urine. It inhibits nitric oxide synthases (NOs) and produces considerable cardiovascular biological effects. Several studies have suggested that plasma concentrations of ADMA provide a marker of risk for endothelial dysfunction and cardiovascular disease. In animal and in population studies ADMA has been associated with progression of CKD. Several mechanisms may be involved in this association, such as compromise of the integrity of the glomerular filtration barrier and development of renal fibrosis. This review summarizes the existing literature on the biology and physiology of ADMA focusing on its role in the progression of renal disease.

Background/Aims/Methods: Aggressive systemic mastocytosis (ASM) is a subtype of systemic mastocytosis, which comprises a heterogenous group of disorders characterized by infiltration of bone marrow, skin, liver, spleen, lymph nodes and gastrointestinal tract by neoplastic mast cells. There is lack of data on the association of ASM with renal involvement, as kidney is not among the known organs affected by ASM. Results/Conclusions: To the best of our knowledge, this is the first case of ASM associated with mesangioproliferative glomerulonephritis and monoclonal gammopathy of undetermined significance, without the presence of nephrotic syndrome. The patient’s clinical course and the intriguing family history, along with the treatment selection are described. Finally, the proposed possible pathophysiological mechanisms explaining the renal involvement of our patient are discussed.

In order to evaluate the role of nifedipine in the nephrotoxic effect induced by both ischemia and CyA, 18 healthy mongrel dogs were used. The kidneys were exposed and subjected to 1 h of ischemia by clamping both renal vessels. To the renal artery of the first group of kidneys (n = 9), 300 mL of cold Euro-Collins solution, in which nifedipine (Bay a 1040-10 mg) was diluted, was infused for 15 min (nifedipine group), while 300 mL of cold Euro-Collins solution plus 10 mg of placebo (Bay a 1040-placebo) was infused to the renal artery of the second group (n = 9) of kidneys (placebo group). Venous drainage was effected through a plastic cannula. All animals received through a nasogastric catheter 20 mg/kg cyclosporine A at the beginning of the ischemia. The 1 h of ischemia was divided in a 15-min period of cold ischemia and 45-min of warm ischemia, at the end of which the clamps were removed. During the 2 h (30 min x 4) after reperfusion, 10 mg of nifedipine and placebo was administered additionally by a peripheral vein to the nifedipine and the placebo group, respectively. Then the kidneys were removed for histological study. Urine volume and creatinine and urea clearances of the nifedipine group were significantly higher than the placebo group (p0.001) while TxB2 levels were higher in the placebo group in all studied periods (p0.001). Urine sodium, FENa, osmolar clearance, and LDH values were significantly different (p0.01), but the urine potassium concentration was not different in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aim: The aim of this study was to examine the validity, reproducibility and internal consistency of a Greek translation of the Kidney Disease Quality of Life-Short Form (KDQOL-SF) questionnaire. Methods: The KDQOL-SF questionnaire was translated from English to Greek and was administered in 240 randomly selected patients undergoing hemodialysis in six Renal Units in Greece. The instrument’s validity was tested by examining the association between patient’s KDQOL-SF scores and comorbidity assessed with the Index of Coexistent Disease. Reproducibility was examined by readministering the questionnaire in 50 randomly selected patients within 1 month. Internal consistency was assessed by estimating Cronbach’s alpha coefficient. Results: Patients were divided into two groups according to the severity of comorbidity assessed with the Index of Coexistent Disease. Those with less comorbid conditions had significantly higher scores in most components of the KDQOL-SF questionnaire, confirming its validity. The correlation coefficients between the two administrations of the instrument ranged from 0.88 to 0.98 for each of the main components, which was above the desired level of 0.85. Cronbach’s alpha coefficient ranged from 0.91 to 0.92 for the various components, values well above the minimum desired 0.70 level. Conclusions: The present study shows that the Greek version of the KDQOL-SF questionnaire has high validity, reproducibility and internal consistency. Production of validated translations of the KDQOL-SF questionnaire in various languages will help promote health-related quality of life of end-stage renal disease patients all over the world.

Observational studies have suggested a causal relationship between hyperhomocysteinemia and cardiovascular complications such as stroke and ischemic heart disease. The Homocysteine Lowering Trialists' Collaboration has shown that daily administration of folic acid can significantly decrease homocysteine levels up to 25%. Aim of this study was to investigate the effect of daily supplementation of folic acid (5 mg) on IMT after 18 months of treatment in patients with at least one cardiovascular risk factor.We enrolled 103 patients with at least one cardiovascular risk factor who were randomized to receive either a daily dose of 5 mg folic acid (group I, n=53) or placebo (group II, n=50) for 18 months.After 18 months of folic acid supplementation, homocysteine levels were significantly reduced in the active treatment group compared to a non-significant increase in the placebo group. Folic acid levels were markedly increased in the former group and non-significantly reduced in the latter. Significant regression of carotid IMT was observed (0.961+/-0.092 to 0.933+/-0.077 mm, p0.001) compared to significant IMT progression in the placebo group (0.964+/-0.099 to 0.984+/-0.094 mm).Folic acid supplementation results in significant IMT reduction after 18 months in patients with at least one cardiovascular risk.

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.

The aim of this study was to estimate the cost-effectiveness of renin-angiotensin-aldosterone system blockers in patients with diabetic nephropathy. A cost-effectiveness analysis was performed based on a meta-analysis of studies investigating the effect of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) as part of a treatment regimen on the incidence of end-stage renal disease (ESRD) in patients with diabetic nephropathy. The primary outcome was the cost to prevent 1 patient from developing ESRD. Cost analysis was performed from a third-party payer perspective in 2006 US dollars. As part of a treatment regimen, ARBs significantly reduced the incidence of ESRD and doubling of serum creatinine concentration (P

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.

The aim of this study was to assess the effect of nifedipine and piracetam alone or in combination in the protection of renal function and morphology after cyclosporin A (CyA) administration. Thirty healthy mongrel dogs with a mean body weight of 15 kg were sacrificed. Six animals (group C) were given CyA 20 mg/kg body weight per os, while the remaining groups (8 animals each) were given concomitantly 20 mg nifedipine (group CN) or 4 g of piracetam (group CP), or both drugs in combination (group CNP). After 5 days of drug administration the animals were anesthetized, both kidneys were exposed, and functional tests were performed. Then the kidneys were removed for histological study. The mean plasma CyA levels in the four groups were 1765 +/- 685 ng/mL, 1300 +/- 324 ng/mL, 1116 +/- 491 ng/mL and 1600 +/- 290 ng/mL, respectively. Urine volume, creatinine, urea, and osmolar clearances were significantly higher in the groups CN, CP, and CNP compared to the control group C (p0.01). Urine sodium concentration was significantly higher (p0.05 or p0.01) in nifedipine groups than in the other two groups of animals, while the fractional excretion of sodium (FENa%) was significantly higher (p0.01) in all treated groups compared to controls. Plasma thromboxane-B2 levels were significantly reduced by each drug alone or in combination (p0.01). Morphological lesions, similar in all groups, did not correlate with the functional improvement.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

SummaryCardiovascular disease is the leading cause of death in Western countries. Since 1969, homocysteine has been implicated in the atherosclerotic process, and numerous observational studies have suggested that hyperhomocysteinaemia should be considered as an independent cardiovascular risk factor. B-vitamins, particularly folic acid, reduce homocysteine levels effectively; it was suggested, therefore, that supplementation with these vitamins might decrease cardiovascular risk and reduce the morbidity and mortality associated with stroke, coronary heart disease and peripheral artery disease. However, the results of clinical trials conducted to investigate this issue have been inconsistent. This review discusses the findings of these trials and provides an updated overview on the ‘homocysteine hypothesis’.

Background:Darbepoetin alfa is an erythropoietis-stimulating glycoprotein with a ∼3-fold longer t1/2 and greater biological activity compared with recombinant human erythropoietin (rHuEPO).Objective:The objective of this study was to evaluate the efficacy andtolerability of long-term (24-week) darbepoetin alfa treatment in maintaining hemoglobin (Hb) concentrations in the target range of 10 to 13 g/dL in patients undergoing dialysis; the patients were switched from rHuEPO to a less-frequent dosing regimen of darbepoetin alfa without an increase in dose.Methods:In this Phase IIlb, open-label, multicenter study, patients withend-stage renal disease (ESRD) undergoing dialysis who were receiving rHuEPO BIW or TIW at baseline were switched to darbepoetin alfa QW; patients receiving rHuEPO QW were switched to darbepoetin alfa Q2W Administration of darbepoetin alfa was by the same route as previous rHuEPO administration (IV or SC). Patients received darbepoetin alfa for 24 weeks, including a 20-week drug titration period followed by a 4-week, stable-dose evaluation period. The mode, dose, and frequency of administration of darbepoetin alfa were compared with those of baseline rHuEPO. Tolerability assessment was based on spontaneous reporting and laboratory tests (hematology, vital sign measurement, iron status, and biochemistry).Results:The study comprised 173 patients who were divided into 2 groups by route of administration (IV group, n = 146; SC group, n = 27). Mean (SE) adjusted increases in Hb concentration from baseline to the evaluation period for patients receiving darbepoetin alfa QW were 0.94 (0.32) g/dL and 0.38 (0.30) g/dL for the IV or SC routes, respectively (P = 0.004 and NS, respectively). For patients receiving darbepoetin alfa Q2W the mean (SE) adjusted increases in Hb concentration were 0.08 (0.53) g/dL and 0.48 (0.35) g/dL for the IV and SC routes, respectively (both, P = NS). No significant differences in IV/SC dose ratio were observed between the 2 routes of administration. In addition, no increases in darbepoetin alfa dose were observed. The most commonly reported adverse events were hypertension (8 patients [5%]) and vascular access thrombosis (4 [2%]). The incidence of treatment-related adverse events was 6 (3%).Conclusions:Darbepoetin alfa effectively maintained Hb concentrations within the target range without an increase in dose, even at a reduced dosing frequency. Overall, darbepoetin alfa was well tolerated.

In an experimental study on six healthy dogs both kidneys were exposed and subjected to 1 h of ischaemia by clamping both renal vessels. To the left renal artery, 300 ml of cold (4 degrees C) Euro-Collins solution in which nifedipine (Bay a 1040--20 micrograms/kg per min) was diluted, was infused for 15 min. Simultaneously 300 ml of cold Euro-Collins solution plus 20 micrograms/kg per min of placebo (Bay a 1040--placebo) was infused in the right renal artery. The 1 h of ischaemia was divided in a 15-min period of cold ischaemia and 45 min of warm ischaemia, at the end of which both clamps were removed. During the 2 h (4 X 30 min) following the removal of the clamps, urine volume, urea and creatinine clearances, urine sodium concentration, sodium fractional excretion (%) and urine/plasma osmolality ratio measurements were made and results compared to the pre-ischaemia values. Both kidneys were then removed for histological study. The nifedipine group restored diuresis of 0.43 +/- 0.23 ml/min within 30 min, while this degree of diuresis (0.64 +/- 0.16 ml/min) was achieved by the placebo group at 120 min. Urine volume as well as creatinine and urea clearances of the nifedipine group were significantly higher in all studied periods compared to the placebo group (P less than 0.01 or P less than 0.025). Urine sodium and FENa (%) were not different between the two groups, and urine/plasma osmolality ratio was above 1.1 in all studied periods for both groups. The microscopic study did not show any significant differences between the two groups. We conclude that nifedipine is effective in the protection of renal function when it is administered during experimental in situ preservation.