Search

Objective The aim of the study was to examine the prevalence of protein-energy wasting (PEW) in hemodialysis (HD) and peritoneal dialysis (PD) patients in our center and determine whether adiponectin and leptin are involved in the development of PEW. Design Prospective (18 months). Setting University Hospital of Heraklion, Crete, Greece. Subjects Seventy-four end-stage-renal-disease patients, 47 on HD and 27 on PD. Main outcome measures At three sequential time points (baseline, 6 and 18 months) anthropometric, nutritional and inflammatory status data were collected. Serum adiponectin and leptin were also assessed at each time point. Patients were allocated to 3 strata according to PEW severity (0, 1–2 and ≥3 criteria for PEW). Results Adiponectin and leptin levels were greater among PD compared to HD patients ( p ≤ 0.035). Adiponectin levels were incrementally greater across increasing strata of PEW ( p ≤ 0.002). Leptin showed the opposite trend, with lower levels in malnourished patients and higher levels in patients with zero PEW criteria ( p ≤ 0.042). Alterations of adiponectin levels during the observation period were dependent on PEW stratum ( p ≤ 0.021) and mode of dialysis ( p ≤ 0.002), after adjustment for age, dialysis vintage, gender and fat mass index. Particularly, adiponectin levels increased over time in HD patients with ≥3 criteria for PEW, whereas adiponectin levels decreased in PD patients with ≥3 criteria for PEW throughout the study. Leptin alterations over time were not affected by dialysis mode or PEW stratification. Conclusions Our study provides evidence that increased adiponectin and decreased leptin levels are independently associated with PEW and thus, poor prognosis.

Estimation of evapotranspiration is always a major component in water resources management. The reliable estimation of daily evapotranspiration supports decision makers to review the current land use practices in terms of water management, while enabling them to propose proper land use changes. Traditional techniques of calculating daily evapotranspiration based on field measurements are valid only for local scales. Earth observation satellite sensors are used in conjunction with Surface Energy Balance (SEB) models to overcome difficulties in obtaining daily evapotranspiration measurements on a regional scale. In this study the SEB System (SEBS) is used to estimate daily evapotranspiration and evaporative fraction over the Nile Delta along with data acquired by the Advance Along Track Scanning Radiometer (AATSR) and the Medium Spectral Resolution Imaging Spectrometer (MERIS), and six in situ meteorological stations. The simulated daily evapotranspiration values are compared against actual ground-truth data taken from 92 points uniformly distributed all over the study area. The derived maps and the following correlation analysis show strong agreement, demonstrating SEBS’ applicability and accuracy in the estimation of daily evapotranspiration over agricultural areas.

Summary Objective To describe our 3-year experience in the long-term efficacy and safety of percutaneous ethanol injection therapy (PEIT), as an alternative to surgery for the management of patients with primary hyperparathyroidism (p-HPT). Design Prospective study with a mean follow-up of 19·6 ± 10·6 months. Patients Our study population included 19 consecutive high risk patients with p-HPT, who met the criteria for surgery. Measurements Under ultrasonic guidance, ethanol (95%) was injected into parathyroid glands with a volume of ≥ 0·15 cm3. With the aim of normalizing intact parathormone (iPTH) values, repeated ethanol injections were carried out, in an interval of 2 weeks, until normalization of iPTH was reached or until no residual blood supply was detected by ultrasound in the gland. Biochemical parameters were monitored throughout the study. Results At 6-month follow-up, normalization of iPTH levels (10–65 ng/l) was achieved in 11 (58%) patients (responders). Of the eight remaining patients (nonresponders), six patients had reduced (but not normalized) iPTH levels and two patients required parathyroid surgery. Seventeen (11 responders and 6 nonresponders) of the 19 patients (89·5%) became normocalcaemic (serum Ca ≤ 2·57 mmol/l) and remained so for a mean follow-up of 21 months (8–39 months). The odds ratio (P 200 ng/l. The only complication was a transient dysphonia noticed in three patients. Conclusions PEIT is a safe and effective nonsurgical treatment for patients with p-HPT, who are unsuitable for surgical intervention.

Listeria monocytogenes has rarely been reported to cause peritonitis in peritoneal dialysis (PD) patients. Listeriosis is usually a severe disease with a mortality rate of 20 to 40% in humans despite early antibiotic treatment. In this report we present the first case in Greece of peritonitis caused by L. monocytogenes, in a chronic PD patient with severe cardiac failure. The patient received prolonged antibiotic therapy with vancomycin and netilmicin which resulted in peritonitis resolution. Unfortunately however, the listeria infection caused decompensation of the patient’s cardiac failure and led to his death, despite appropriate antibiotic treatment. When peritoneal fluid cultures yield gram positive rods in an immune-compromised patient or on a patient with severe underlying diseases who regularly consumes dairy products, the clinical suspicion of this rare infection must be immediately evaluated. Listeriosis can be fatal despite effective antibiotic therapy, since it affects patients with severe underlying pathologies.

The AKT-mTOR pathway is activated in diabetic nephropathy. Renin-angiotensin system modulators exert beneficial effects on the diabetic kidney. We explored the action of losartan on AKT-mTOR phosphorylation in glomeruli and podocytes. Diabetes mellitus was induced to Sprague-Dawley rats by streptozotocin. Five months later, the rats were commenced on losartan and euthanized 2 months later. Kidneys were processed for immunofluorescence studies. Glomeruli were isolated for Western blot analysis. Diabetes increased activated forms of AKT and mTOR both in glomeruli and podocytes. In diabetic rats, losartan decreased phosphorylated/activated forms of AKT (Thr308) and mTOR (Ser2448) in glomeruli but decreased only activated mTOR in podocytes. However, in both glomeruli and podocytes of healthy animals, an inverse pattern was evident. In conclusion, a new body of evidence indicates the differential activation of AKT-mTOR in glomeruli and podocytes of healthy and diabetic animals in response to losartan.

Familial amyloid polyneuropathy is characterized by transthyretin (TTR) deposition in various tissues, including the kidneys. While deposition induces organ dysfunction, renal involvement in TTR-related amyloidosis could manifest from proteinuria to end-stage kidney failure. As proteinuria is considered result of glomerular filtration barrier injury we investigated whether TTR deposition affects either glomerular basement membrane (GBM) or podocytes.Immunohistochemistry, immunoblot and gene expression studies for nephrin, podocin and WT1 were run on renal tissue from human-TTRV30M transgenic mice hemizygous or homozygous for heat shock factor one (Hsf-1). Transmission electron microscopy was used for evaluation of podocyte foot process width (PFW) and GBM thickness in Hsf-1 hemizygous mice with or without TTRV30M or amyloid deposition.Glomeruli of hsf-1 hemizygous transgenic mice showed lower nephrin and podocin protein levels but an increased podocyte number when compared to Hsf-1 homozygous transgenic mice. Nephrin, podocin and WT1 gene expression levels were unaffected by the Hsf-1 carrier status. TTRV30M deposition was associated with increased PFW and GBM thickness.Under the effect of Hsf-1 hemizygosity, TTRV30M deposition has deleterious effects on GBM thickness, PFW and slit diaphragm composition, without affecting nephrin and podocin gene expression.

Transthyretin related amyloidosis is a nosological entity that leads to disability, diminished quality of life, all stages of chronic kidney disease and eventually death. Podocytes are polarized, highly differentiated epithelial cells important for proper nephron function. In the present study we investigated whether deposited TTRVal30Met (TTRV30M) molecules could be localized within podocytes in situ under the effect of different housing conditions (i.e. specific pathogen free [SPF] vs. non-SPF). Murine renal glomeruli from human TTRV30M (hTTRV30M) transgenic mice were examined via direct and indirect immunofluorescence techniques for the presence of hTTRV30M, murine serum amyloid P, activated caspase-3 and NPHS1. Association strength and amount of colocalization for NPHS1-hTTRV30M, NPHS1-activated caspase-3, hTTRV30M-murine serum amyloid P were estimated. Localization of hTTRV30M in podocytes was demonstrated by immuno-electron microscopy. Renal hTTRV30M gene and NPHS1 gene expression levels were estimated. Non-SPF transgenic mice showed increased glomerular hTTRV30M deposition compared to their SPF counterparts. Furthermore increased podocytic localization of hTTRV30M was noticed in non-SPF mice. Glomerular caspase-3 activation was increased only in the non SPF housing conditions. Podocytic caspase-3 activation was increased in SPF and in non-SPF transgenic mice when compared to non transgenic controls. Environmental conditions influence glomerular deposition and podocytic localization of hTTRV30M. In this context increased caspase-3 activation occurred.

Background. In the normal kidney, rapamycin is considered to be non-nephrotoxic. In the present study, we investigated whether rapamycin is indeed non-nephrotoxic by examining the ultrastructural and molecular alterations of podocytes in healthy mice. Methods. Balb/c mice were given three different intraperitoneal doses of rapamycin for 1 week (dose model)— low-dose group: 1 mg/kg/day, intermediate-dose (ID) group: 1.5 mg/kg/day and high-dose (HD) group: 3 mg/kg/day; four mice in each group. An ID of rapamycin was also given for three different periods (time model): 1, 4 and 8 weeks; four mice were in each group. Mice treated with dimethyl sulphoxide served as controls. Body weight was measured weekly. Renal function was assessed by serum creatinine at the time of sacrifice. For estimation of albuminuria, 24h urine collections were performed before treatment and weekly thereafter. Glomerular content of nephrin, podocin, Akt and Ser473-phospho-Akt was estimated by western blot and immunofluorescence. Nephrin and podocin messenger RNA (mRNA) were measured by real-time polymerase chain reaction. Mean podocyte foot process width (FPW) was measured by electron microscopy. Results. Urine albumin levels increased in the HD and 4-week groups. Renal function was modestly deteriorated in the HD group. The mean FPW increased in a dose-dependant manner at Week 1, further deteriorated at Week 4 and finally improved at Week 8. Nephrin and podocin mRNA levels showed a significant decrease at Week 1 and were restored at Week 4 and 8. Nephrin and podocin protein levels were reduced at Week 4 and recovered at Week 8. Ser473phospho-Akt significantly increased in all rapamycintreated groups. Conclusions. Rapamycin induced significant ultrastructural and molecular alterations in podocytes in association with albuminuria. These alterations happened early during treatment and they tended to improve over an 8-week treatment period.

Background Adiponectin (ADPN) is the most abundant adipocyte-specific cytokine that plays an important role in energy homeostasis by regulating lipid and glucose metabolism. Studies of the impact of ADPN on clinical outcomes have yielded contradictory results so far. Here, we examined the association of ADPN with serum magnesium (s-Mg) and calcium (s-Ca) levels and explored the possibility whether these two factors could modify the relationship between ADPN and all-cause mortality in patients with end-stage renal disease. Methodology/Principal Findings After baseline assessment, 47 hemodialysis and 27 peritoneal dialysis patients were followed- up for a median period of 50 months. S-Mg and s-Ca levels emerged as positive and negative predictors of ADPN levels, respectively. During the follow-up period 18 deaths occurred. There was a significant 4% increased risk for all-cause mortality for each 1-µg/ml increment of ADPN (crude HR, 1.04; 95% CI, 1.01–1.07), even after adjustment for s-Mg and s-Ca levels, dialysis mode, age, albumin and C-reactive protein. Cox analysis stratified by s-Mg levels (below and above the median value of 2.45 mg/dl) and s-Ca levels (below and above the median value of 9.3 mg/dl), revealed ADPN as an independent predictor of total mortality only in the low s-Mg and high s-Ca groups. Furthermore, low s-Mg and high s-Ca levels were independently associated with malnutrition, inflammation, arterial stiffening and risk of death. Conclusions/Significance The predictive value of ADPN in all-cause mortality in end-stage renal disease patients appears to be critically dependent on s-Mg and s-Ca levels. Conversely, s-Mg and s-Ca may impact on clinical outcomes by directly modifying the ADPN’s bioactivity.

Introduction The kidney is increasingly recognised as a target organ of chronic graft-versus-host disease after hematopoietic cell transplantation in the context of the development of the nephrotic syndrome. Chronic graft-versus-host disease is associated with autoimmune phenomena similar, but not identical, to those observed in various rheumatologic disorders, implicating autoimmunity as an important component of the disease. Case presentation We report the case of a 57-year-old Caucasian man who developed the nephrotic syndrome due to membranous nephropathy in association with recurrent chronic graft-versus-host disease, along with a lupus-like syndrome manifested with pancytopenia, hair loss, positive anti-DNA antibodies and sub-epithelial and mesangial immune deposits. To the best of our knowledge, this is the first case reported in the literature. The nephrotic syndrome subsided soon after he was treated with a short course of cyclosporin with steroids. Unfortunately he died seven months later due to a relapse of leukemia. Conclusions Our case report confirms the notion that chronic graft-versus-host disease is characterized by the appearance of autoimmune phenomena similar, but not identical, to those seen in autoimmune diseases. The decision for more immunosuppression has to be weighed against the need for preservation of the graft versus leukemia phenomenon.

Background The mammalian target of rapamycin (mTOR) inhibitor, rapamycin, has been shown to inhibit the progression of murine lupus nephritis by virtue of its potent immunosuppressive properties. The phosphoinositol-3-kinase (PI3K)/Akt pathway is a major upstream activator of mTOR and has been implicated in the propagation of cancer and autoimmunity. However, the activation status of the PI3K/Akt/mTOR pathway in lupus nephritis has not been studied so far. Methods In NZBW/F1 female mice, we examined the glomerular expression of Akt and mTOR by immunofluorescence and western blot. We also searched for specific phosphorylations of these kinases known to ensue during activation of the PI3K/Akt/mTOR pathway. In parallel, we examined the therapeutic role of rapamycin either before or after the development of overt lupus nephritis. Results We found that in untreated mice, as opposed to healthy controls, Akt and mTOR were over-expressed and phosphorylated at key activating residues. Rapamycin prolonged survival, maintained normal renal function, normalized proteinuria, restored nephrin and podocin levels, reduced anti-dsDNA titres, ameliorated histological lesions, and reduced Akt and mTOR glomerular expression activation. Conclusions These results suggest that: (i) the PI3K/Akt/mTOR pathway is upregulated in murine lupus nephritis, thus justifying treatment with rapamycin; (ii) rapamycin not only blocks mTOR but also negatively regulates the PI3K/Akt/mTOR pathway; and (iii) rapamycin is an effective treatment of murine lupus nephritis. Examination of the PI3K/Akt/mTOR pathway may offer new insights into the pathogenesis of lupus nephritis in humans and may lead to more individualized and less toxic treatment.

Considerable controversy currently exists in the literature concerning the mode of catheter placement and its impact on the technical success of peritoneal dialysis (PD). We decided to compare the impact of the surgical versus the percutaneous insertion technique on peritoneal dialysis catheter (PDCs) complications and survival. Our study population comprised 152 patients in whom 170 PDCs were inserted between January 1990 and December 2007 at the main PD unit on the island of Crete. Eighty four catheters were surgically placed (S group) and 86 were placed percutaneously by nephrologists (N group). The total experience accumulated was 4997 patient-months. The overall complications did not differ between the two groups. Only early leakage was more frequent in N group than S group (10.3 versus 1.9 episodes per 1000 patient-months; p < 0.001). However, it was easily treated and did not constitute a cause of early catheter removal. Catheter survival was 91.1%, 80.7%, and 73.2%, in the S group versus 89.5%, 83.7%, and 83.7% for the N group at 1, 2, and 3 years, respectively (p = 0.2). Catheter survival has significantly increased over the last decade. Factors positively affecting PDC survival appeared to be the use of mupirocin for exit site care and the utilization of the coiled type of catheter, practices implemented mainly after 1999. Peritonitis-free survival and patient survival were not associated with the mode of placement, while in Cox regression analysis, were longer in patients treated with automated PD. The placement mode did not affect PD outcomes. Percutaneous implantation proved a safe, simple, low cost, immediately available method for PDC placement and helped to expand our PD program.

In this paper we present a pedagogically-documented approach and model that facilitates the specialised and personalised e-training of professionals and end-users in application software products. The main focus of our methodology is on blended learning, authentic learning and competence based learning. Via blended learning, face to face as well as online teaching is used. Moreover, there is an e-training solution that can be used either as stand alone solution, for teaching a particular competence or can be used as a support to face to face teaching (that is revisit a competence taught in face to face). The e-Training component of the ELEVATE environment uses authentic learning by utilising “live” software systems. Competence based learning is used to identify the competence gap as well as tailor the training that the individual learner needs to attain the competence required.

Background Oxidative stress may play a critical role in the vascular disease of end stage renal failure and hemodialysis patients. Studies, analyzing either discrete analytes and antioxidant substances, or the integrated total antioxidant activity of human plasma during hemodialysis, give contradictory results. Methods Recently, we have introduced a new automated method for the determination of Total Antioxidant Capacity (TAC) of human plasma. We have serially measured TAC and corrected TAC (cTAC: after subtraction of the interactions due to endogenous uric acid, bilirubin and albumin) in 10 patients before the onset of the dialysis session, 10 min, 30 min, 1 h, 2 h and 3 h into the procedure and after completion of the session. Results Our results indicate that TAC decreases, reaching minimum levels at 2 h. However, corrected TAC increases with t1/2 of about 30 min. We then repeated the measurements in 65 patients undergoing dialysis with different filters (36 patients with ethylene vinyl alcohol copolymer resin filter -Eval-, 23 patients with two polysulfone filters -10 with F6 and 13 with PSN140-, and 6 patients with hemophan filters). Three specimens were collected (0, 30, 240 min). The results of this second group confirm our initial results, while no significant difference was observed using either filter. Conclusions Our results are discussed under the point of view of possible mechanisms of modification of endogenous antioxidants, and the interaction of lipid- and water-soluble antioxidants.

ObjectivesThe objective of this study was to identify the epidemiological, clinical, and microbiological factors affecting the outcome of peritoneal dialysis (PD)-associated peritonitis.MethodsAll patients with PD-associated peritonitis, cared for at the University Hospital of Heraklion from 1990 to 2007, were retrospectively studied.ResultsA total of 247 episodes of PD-associated peritonitis occurring in 82 patients were evaluated. The median age of patients was 68 years (range 10–92 years); 51 (62%) were males. There were 104 episodes (42%) of Gram-positive peritonitis, 46 (19%) of Gram-negative peritonitis, 13 (5%) of polymicrobial peritonitis, and 11 (4%) of fungal peritonitis. There were 64 (26%) complicated episodes. The latter included 22 (8.9%) relapses, 13 (5.3%) repeated episodes, 18 (7.3%) catheter removals, and 11 (4.5%) deaths. In multivariate analysis, the presence of a purulent exit-site infection (p100×106/l for more than 5 days (p100×106/l, prior use of antimicrobials, and low serum total protein level are potential predictors of complicated PD-associated peritonitis and may distinguish high-risk cases.