Differential effects of biocompatible peritoneal dialysis fluids on human mesothelial and endothelial cells in 2D and 3D phenotypes.

INTRODUCTION: Peritoneal dialysis (PD) is a life maintaining treatment in patients with end-stage renal disease. Its chronic application leads to peritoneal mesothelial layer denudation and fibrotic transformation along with vascular activation of inflammatory pathways. The impact of different PD fluids (PDF) on mesothelial and endothelial cell function and repair mechanisms are not comprehensively described. MATERIALS AND METHODS: Mesothelial (MeT-5A) and endothelial cells (EA.hy926) were cultured in 1:1 ratio with cell medium and different PDF (icodextrin-based, amino acid-based, and glucose-based). Cell adhesion, cell migration, and cell proliferation in 2D and spheroid formation and collagen gel contraction assays in 3D cell cultures were performed. RESULTS: Cell proliferation and cell-mediated gel contraction were both significantly decreased in all conditions. 3D spheroid formation was significantly reduced with icodextrin and amino acid PDF, but unchanged with glucose PDF. Adhesion was significantly increased by amino acid PDF in mesothelial cells and decreased by icodextrin and amino acid PDF in endothelial cells. Migration capacity was significantly decreased in mesothelial cells by all three PDF, while endothelial cells remained unaffected. CONCLUSIONS: In 3D phenotypes the effects of PDF are more uniform in both mesothelial and endothelial cells, mitigating spheroid formation and gel contraction. On the contrary, effects on 2D phenotypes are more uniform in the icodextrin and amino acid PDF as opposed to glucose ones and affect mesothelial cells more variably. 2D and 3D comparative assessments of PDF effects on the main peritoneal membrane cell barriers, the mesothelial and endothelial, could provide useful translational information for PD studies.

Different patterns of changes in free 25-hydroxyvitamin D concentrations during intermittent fasting among meat eaters and non-meat eaters and correlations with amino acid intake.

We prospectively assessed changes in free 25-hydroxyvitamin D [25(OH)D] and vitamin D binding protein (VDBP) among overweight adults who followed a pescatarian Orthodox intermittent fasting regimen (n = 59) and controls who followed a low-fat 12:12 diet (n = 46). Total and free 25(OH)D, parathyroid hormone, VDBP, anthropometric data, and amino acid intake were evaluated in both groups at three time points: at baseline, 7 weeks after diet implementation, and 5 weeks after participants returned to their usual eating habits (12 weeks from baseline). An increase in amino acid intake between baseline and 12 weeks was independently correlated with higher free 25(OH)D values at 12 weeks for both groups. Our findings suggest that diet can affect free 25(OH)D concentrations, through variations in amino acid intake, independently of exposure to sunlight, providing novel mechanistic insights into the future planning of vitamin D supplementation strategies. However, this hypothesis needs to be tested in larger studies.

Epidemiology of Hypertension among Patients on Peritoneal Dialysis Using Standardized Office and Ambulatory Blood Pressure Recordings.

INTRODUCTION: Prior studies conducted in peritoneal dialysis (PD) patients in the late 1990s provided considerably variable estimates of the prevalence and control of hypertension. The present study aimed to investigate the current state of hypertension management in this high-risk population. METHODS: In 140 stable PD patients, we performed standardized automated office blood pressure (BP) measurements and 24-h ambulatory BP monitoring (ABPM) using the Mobil-O-Graph device (IEM, Germany). Office and ambulatory hypertension was diagnosed in patients with office BP ≥140/90 mm Hg and 24-h BP ≥130/80 mm Hg, respectively. Patients treated with ≥1 BP-lowering medications were also classified as hypertensives. RESULTS: The prevalence of office and ambulatory hypertension was 92.9% and 95%, respectively. In all, 92.1% of patients were being treated with an average of 2.4 BP-lowering medications daily. Adequate BP control was achieved in 52.3% and 38.3% of hypertensives by office BP and ABPM, respectively. The agreement between these 2 techniques in the identification of patients with BP levels above the diagnostic thresholds of hypertension was moderate (k-statistic: 0.524). In all, 5% of patients were normotensives with both techniques, 31.4% had controlled hypertension, 5% had white-coat hypertension, 19.3% had masked hypertension, and 39.3% had sustained hypertension. Isolated nocturnal hypertension was detected in 23.6% of patients, whereas no patient had isolated daytime hypertension. CONCLUSION: Among PD patients, hypertension is highly prevalent and remains often inadequately controlled. The use of ABPM enables the better classification of severity of hypertension and identification of isolated nocturnal hypertension, which is a common BP phenotype in the PD population.

Contemporary Data on the Status and Medical Management of Acute Heart Failure.

PURPOSE OF REVIEW: Acute heart failure (AHF) is among the leading causes for unplanned hospital admission. Despite advancements in the management of chronic heart failure, the prognosis of AHF remains poor with high in-hospital mortality and increased rates of unfavorable post-discharge outcomes. With this review, we aim to summarize current data on AHF epidemiology, focus on the different patient profiles and classifications, and discuss management, including novel therapeutic options in this area. RECENT FINDINGS: There is significant heterogeneity among patients admitted for AHF in their baseline characteristics, heart failure (HF) aetiology and precipitating factors leading to decompensation. A novel classification scheme based on four distinct clinical scenarios has been included in the most recent ESC guidelines, in an effort to better risk stratify patients and guide treatment. Intravenous diuretics, vasodilators, and inotropes remain the cornerstone of management in the acute phase, and expansion of use of mechanical circulatory support has been noted in recent years. Meanwhile, many treatments that have proved their value in chronic heart failure demonstrate promising results in the setting of AHF and research in this field is currently ongoing. Acute heart failure remains a major health challenge with high in-hospital mortality and unfavorable post-discharge outcomes. Admission for acute HF represents a window of opportunity for patients to initiate appropriate treatment as soon as possible after stabilization. Future studies are needed to elucidate which patients will benefit the most by available therapies and define the optimal timing for treatment implementation.

Implementation of Christian Orthodox fasting improves plasma adiponectin concentrations compared with time-restricted eating in overweight premenopausal women.

The exact mechanisms mediating the metabolic effects of Orthodox fasting remain unclear. Plasma adiponectin, biochemical and anthropometrical data were evaluated in 55 Orthodox fasters (OF) and 42 time-restricted eating controls (all women, mean age 47.8 years) at three time points: baseline, end of the dietary intervention (7 weeks) and 5 weeks after participants returned to their typical dietary habits (12 weeks from baseline). In the OF group, there was an increase in adiponectin values at 12 weeks compared with baseline (9815.99 vs 8983.52 mg/ml, p = 0.02) and a reduction in body fat mass between baseline and 12 weeks (35.44 vs 32.17%, p = 0.004) and between 7 and 12 weeks (35.33 vs 32.17%, p = 0.003). In the same group, an inverse correlation between adiponectin and waist circumference values was observed over the entire study period. Our results provide novel evidence that Orthodox fasting has favourable metabolic effects related to improved adiponectin concentrations.

Intestinal SGLT1 as a therapeutic target in COVID-19-related diabetes: A "two-edged sword" hypothesis.

Emerging data are linking coronavirus disease 2019 (COVID-19) with an increased risk of developing new-onset diabetes. The gut has been so far out of the frame of the discussion on the pathophysiology of COVID-19-induced diabetes, with the pancreas, liver, and adipose tissue being under the spotlight of medical research. Sodium-glucose co-transporters (SGLT) 1 represent important regulators of glucose absorption, expressed in the small intestine where they mediate almost all sodium-dependent glucose uptake. Similar to what happens in diabetes and other viral infections, SGLT1 upregulation could result in increased intestinal glucose absorption and subsequently promote the development of hyperglycaemia in COVID-19. Considering the above, the question whether dual SGLT (1 and 2) inhibition could contribute to improved outcomes in such cases sounds challenging, deserving further evaluation. Future studies need to clarify whether putative benefits of dual SGLT inhibition in COVID-19 outweigh potential risks, particularly with respect to drug-induced euglycaemic diabetic ketoacidosis, gastrointestinal side effects, and compromised host response to pathogens.

Opportunistic screening for hypertension in the general population in Greece: International Society of Hypertension May Measurement Month 2019.

Hypertension remains a major public health issue with inadequate control worldwide. The May Measurement Month (MMM) initiative by the International Society of Hypertension was implemented in Greece in 2019 aiming to raise hypertension awareness and control. Adult volunteers (≥18 years) were recruited through opportunistic screening in five urban areas. Information on medical history and triplicate sitting blood pressure (BP) measurements were obtained using validated automated upper-arm devices. Hypertension was defined as systolic BP ≥140 mmHg and/or diastolic ≥90 mmHg, and/or self-reported use of drugs for hypertension. A total of 5727 were analysed [mean age 52.7 (SD 16.6) years, men 46.5%, 88.3% had BP measurement in the last 18 months]. The prevalence of hypertension was (41.6%) and was higher in men and in older individuals. Among individuals with hypertension, 78.7% were diagnosed, 73.1% treated, and 48.3% controlled. Awareness, treatment, and control of hypertension were higher in women and in older individuals. Hypertensives had a higher body mass index (BMI) and were more likely to have diabetes, myocardial infarction and stroke, and less likely to smoke than normotensives (all P < 0.001). Among treated hypertensives, 65.1% were on monotherapy, and with increasing number of antihypertensive drugs the BP levels were higher and hypertension control rates lower. The prevalence of hypertension in Greece is high, with considerable potential for improving awareness, treatment, and control. Screening programmes, such as MMM, need to be widely implemented at the population level, together with training programmes for healthcare professionals aiming to optimise management and control.

Similar late effects of a 7-week orthodox religious fasting and a time restricted eating pattern on anthropometric and metabolic profiles of overweight adults.

A hypocaloric diet, based on Orthodox fasting (OF) was followed by 29 overweight adults. A low-calorie, 16/8, time restricted eating (TRE) pattern was followed by 16 age- and weight-matched participants. Anthropometric, lipid, glycaemic and inflammation markers were assessed at baseline, at the end of the intervention (7 weeks from baseline) and 6 weeks after the cessation of diets (13 weeks from baseline). There was a trend of weight loss in both groups, which was evident at week 7 (TRE: -2.1 ± 1.0; OF: -2.0 ± 0.5 kg, p < 0.001 from baseline) and remained significant at week 13 (TRE: -2.9 ± 0.7; OF: -2.6 ± 0.3 kg, p < 0.001 from baseline). In the OF group, lipid concentrations declined at week 7 compared with baseline, increasing at week 13 compared with week 7. Our findings suggest that OF promotes a decrease in lipid concentrations, which however, is not evident 6 weeks after its end.

Effects of orthodox religious fasting versus combined energy and time restricted eating on body weight, lipid concentrations and glycaemic profile.

For seven weeks, 37 overweight adults followed a hypocaloric diet based on Orthodox Fasting (OF). A hypocaloric, time restricted eating (TRE) plan (eating between 08:00 to 16:00 h, water fasting from 16:00 to 08:00 h) was followed by 23 Body Mass Index (BMI)-matched participants. Anthropometric, glycaemic and inflammation markers and serum lipids were assessed before and after the diets. Both OF and TRE groups demonstrated reductions in BMI (28.54 ± 5.45 vs 27.20 ± 5.10 kg/m2, p < 0.001 and 26.40 ± 4.11 vs 25.81 ± 3.78 kg/m2 p = 0.001, respectively). Following the intervention, the OF group presented lower concentrations of total and low-density lipoprotein-cholesterol, compared with the pre-fasting values (178.40 ± 34.14 vs 197.17 ± 34.30 mg/dl, p < 0.001 and 105.89 ± 28.08 vs 122.37 ± 29.70 mg/dl, p < 0.001, respectively). Neither group manifested significant differences in glycaemic and inflammatory parameters. Our findings suggest that OF has superior lipid lowering effects than the TRE pattern.

Aggravated Dental and Periodontal Status in Patients with Sickle Cell Disease and Its Association with Serum Ferritin.

AIM: The present study aimed to evaluate the possible consequences of sickle cell disease (SCD) on dental and periodontal health in middle-aged patients and to examine the association of certain cardiovascular parameters and serum ferritin with the dental and periodontal status. MATERIALS AND METHODS: Thirty-seven patients (mean age 43.2 years old) with SCD and 30 non-SCD and otherwise healthy individuals (mean age 38.9 years old) were examined for caries experience and periodontal status in addition to cardiovascular characteristics and ferritin level in serum. RESULTS: Compared to controls, SCD patients exhibited higher plaque and gingival bleeding scores, higher prevalence of periodontal diseases, and higher caries experience. Multiple stepwise linear regression analysis showed that caries experience was predominantly determined by the presence of SCD and the age, while major determinants of periodontitis were the ferritin levels and the male gender. The results reveal an aggravation of oral health in SCD patients regarding both caries and periodontal diseases. CONCLUSION: A potential role of the increased central inflammatory response, reflected by the elevated ferritin level in serum, is suggested for the impaired periodontal health of SCD patients. CLINICAL SIGNIFICANCE: Compliance with precautionary dental checks and early management of dental complications is of great importance in order to improve oral health status and prevent general health complications in SCD patients.

Prevalence and control of hypertension among patients on haemodialysis.

BACKGROUND: Earlier studies provided considerably variable estimates on the prevalence and control rates of hypertension in haemodialysis because of their heterogeneity in definitions and blood pressure (BP) measurement techniques applied to detect hypertension. MATERIALS AND METHODS: In this cross-sectional study, 116 clinically stable haemodialysis patients from 3 dialysis centres of Northern Greece underwent home BP monitoring for 1 week with the validated automatic device HEM-705 (Omron, Healthcare). Routine BP recordings taken before and after dialysis over 6 consecutive sessions were also prospectively collected and averaged. Hypertension was defined as: (a) 1-week averaged home BP ≥ 135/85 mm Hg; (b) 2-week averaged predialysis BP ≥ 140/90 mm Hg; and (c) 2-week averaged postdialysis BP ≥ 130/80 mm Hg. Participants on treatment with ≥1 antihypertensives were also classified as hypertensives. RESULTS: The prevalence of hypertension was 88.8% by home, 86.2% by predialysis and 91.4% by postdialysis BP recordings. In all, 96 participants (82.7%) were being treated with an average of 2.0 ± 1.1 antihypertensive medications. Among drug-treated participants, 32.6% were controlled by home, 50.5% by predialysis and 45.3% by postdialysis BP recordings. In multivariate logistic regression analysis, greater use of antihypertensive medications and postdialysis overhydration, assessed with bioimpedance spectroscopy, were both independently associated with higher odds of inadequate home BP control. CONCLUSIONS: This study shows that the prevalence, but mainly the control rates of hypertension in patients on haemodialysis, differs between peridialytic and interdialytic BP recordings. Therefore, the wider use of home BP monitoring may improve the determination of BP control status in this high-risk population.

Thrombophilia in hemodialysis patients: Transfer to peritoneal dialysis is life saving.

The majority of vascular access thrombosis episodes in hemodialysis patients are due to anatomic abnormalities. Thrombophilias are inherited, acquired or mixed disorders which also predispose to venous thromboembolism. They include protein C, protein S and antithrombin deficiencies, as well as gene mutations for prothrombin and factor V Leiden. The most important of the mixed cases is hyperhomocysteinemia, which includes both a genetic and an acquired substrate. We report two patients undergoing hemodialysis who suffered from multiple thrombotic events, the first due to factor V Leiden heterozygosity and the second because of hyperhomocysteinemia due to homozygosity for MTHFR C677T mutation. As no site for vascular access was left, transfer to peritoneal dialysis for both patients improved solute clearance and quality of life with no additional thrombotic events noted.

10-year-long survival in a PD patient with severe calcifying encapsulating peritoneal sclerosis treated with tamoxifen: a case-report.

BACKGROUND: Encapsulating-peritoneal-sclerosis (EPS) is a rare, but serious and life-threatening complication of peritoneal dialysis (PD). Treatment of EPS consists of discontinuation of PD and maintenance of nutritional status, whereas the role of corticosteroids, tamoxifen and other immunosuppresive agents is not yet fully elucidated. CASE-PRESENTATION: We report the case of a 28-year-old patient, who developed a severe form of calcifying EPS after a 6-year-long therapy with automated PD. The clinical presentation was severe with repeated episodes of total bowel obstruction, weight loss and malnutrition that mandated his prolonged hospitalization. Initial treatment included corticosteroids and tamoxifen (20 mg/day) with a clinically meaningful improvement in gastrointestinal function and nutritional status over the first 6-12 months. Corticosteroids were discontinued at 18 months, but owing to persistence of calcifying lesions and peritoneal thickening in repeated computed-tomography (CT) scans, tamoxifen remained unmodified at a low-dose of 20 mg/day for a 10-year-long period. During follow-up, the patient remained symptoms-free in an excellent clinical condition and the CT findings were unchanged. CONCLUSIONS: Long-term administration of tamoxifen was not accompanied by any drug-related adverse effects and potentially exerted a beneficial action on down-regulation of inflammatory and fibrotic processes and improvement of gastrointestinal function, nutritional status and overall health-related quality of life.

The use of sodium-glucose co-transporter 2 inhibitors in the inpatient setting: Is the risk worth taking?

WHAT IS KNOWN AND OBJECTIVE: In the outpatient setting, sodium-glucose co-transporter 2 inhibitors (SGLT2i) are recognized as effective agents to optimize glycaemia and also developing robust evidence for cardiovascular (CV) and renal protection in people with type 2 diabetes, particularly those at higher risk. However, data on the safety and efficacy of these drugs in hospitalized patients remain limited. The purpose of this review is to discuss the balance between risks and benefits of SGLT2i use in the inpatient setting. METHODS: PubMed, Embase and Google Scholar databases were searched to identify relevant published work. Available evidence on the mechanisms of action and the safety profile of SGLT2i in the context of their use in hospitalized individuals are summarized and discussed in this narrative review. RESULTS AND DISCUSSION: The rationale behind the use of these agents in the inpatient setting is based on the low risk of hypoglycaemia, the practical dosing scheme and the potential to decrease subsequent heart failure admission rates. In addition, data from animal studies indicate the ability of SGLT2i to ameliorate oxidative stress, suppress sympathetic activity, enhance autophagy and promote cardiac remodelling, when administered in the acute phase of CV episodes. On the other hand, these drugs have been linked to specific adverse events related to their mechanism of action, including an increased risk of euglycaemic diabetic ketoacidosis and volume depletion, which raises concerns over their usefulness in inpatients, particularly individuals with multimorbidities. WHAT IS NEW AND CONCLUSION: Potential benefits deriving from the use of SGLT2i in the inpatient setting cannot mitigate possible risks, at least until robust evidence on their efficacy in hospitalized individuals become available. The concept of administering these agents in the acute phase of CV episodes, in people with or without diabetes, requires further evaluation in appropriately designed clinical studies.

Wave reflections and systemic vascular resistance are stronger determinants of pulse pressure amplification than aortic stiffness in drug-naïve hypertensives.

Background: Aortic-to-brachial pulse pressure (PP) amplification is a novel biomarker that prognosticates the cardiovascular risk above and beyond central aortic and brachial blood pressure. This phenomenon is modulated by left ventricular contractility and chronotrophy, large-artery stiffness and reflecting properties of microcirculation. However, the relative importance of these parameters as hemodynamic determinant of PP amplification remains elusive.Methods: A total of 88 consecutive drug-naïve hypertensives underwent a non-invasive assessment of central and peripheral hemodynamics via impedance cardiography and pulse wave analysis. Participants were classified into tertiles according to the magnitude of PP amplification. Hemodynamic determinants of low PP amplification were explored in univariate and multivariate regression analysis.Results: Compared with the high tertile, patients within the low PP amplification tertile were older and more commonly female and had lower height, weight and heart rate. Augmentation index (AIx) and systemic vascular resistance index (SVRI) were higher among patients within the low PP amplification tertile, whereas aortic pulse wave velocity (PWV) did not differ among groups. In multivariate analysis, higher AIx (OR: 1.27; 95% CI: 1.09-1.48) and higher SVRI were independently associated with higher odds for low PP amplification, whereas higher heart rate was the only parameter related to lower odds for low PP amplification (OR: 0.84; 95% CI: 0.71-0.99).Conclusion: This study shows that among newly-diagnosed drug-naïve hypertensives, elevated wave reflections and systemic vascular resistance are stronger determinants of PP amplification than aortic stiffness.

Stroke Incidence and Outcomes in Northeastern Greece: The Evros Stroke Registry.

BACKGROUND AND PURPOSE: Data are scarce on both stroke incidence rates and outcomes in Greece and in rural areas in particular. We performed a prospective population-based study evaluating the incidence of first-ever stroke in the Evros prefecture, a region of a total 147 947 residents located in North Eastern Greece. METHODS: Adult patients with first-ever stroke were registered during a 24-month period (2010-2012) and followed up for 12 months. To compare our stroke incidence with that observed in other studies, we standardized our incidence rate data according to the European Standard Population, World Health Organization, and Segi population. We also applied criteria of data quality proposed by the Monitoring Trends and Determinants in Cardiovascular Disease project. Stroke diagnosis and classification were performed using World Health Organization criteria on the basis of neuroimaging and autopsy data. RESULTS: We prospectively documented 703 stroke cases (mean age: 75±12 years; 52.8% men; ischemic stroke: 80.8%; intracerebral hemorrhage: 11.8%; subarachnoid hemorrhage: 4.4%; undefined: 3.0%) with a total follow-up time of 119 805 person-years. The unadjusted and European Standard Population-adjusted incidences of all strokes were 586.8 (95% confidence interval [CI], 543.4-630.2) and 534.1 (95% CI, 494.6-573.6) per 100 000 person-years, respectively. The unadjusted incidence rates for ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage were 474.1 (95% CI, 435-513), 69.3 (95% CI, 54-84), and 25.9 (95% CI, 17-35) per 100 000 person-years, respectively. The corresponding European Standard Population-adjusted incidence rates per 100 000 person-years were 425.9 (95% CI, 390.9-460.9), 63.3 (95% CI, 49.7-76.9), and 25.8 (95% CI, 16.7-34.9) for ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage, respectively. The overall 28-day case fatality rate was 21.3% (95% CI, 18.3%-24.4%) for all strokes and was higher in hemorrhagic strokes than ischemic stroke (40.4%, 95% CI, 31.3%-49.4% versus 16.2%, 95% CI, 13.2%-19.2%). CONCLUSIONS: This is the largest to date population-based study in Greece documenting one of the highest stroke incidences ever reported in South Europe, highlighting the need for efficient stroke prevention and treatment strategies in Northeastern Greece.

The role of the NLRP3 inflammasome and the activation of IL-1ß in the pathogenesis of chronic viral hepatic inflammation.

BACKGROUND AND AIMS: Chronic viral hepatitis is a prevalent disease with major health implications. Its underlying pathophysiological mechanisms are not fully understood. IL-1ß and the NLRP3 inflammasome involvement has been suggested in recent years, from in vitro data and data from peripheral blood samples. Therefore, we investigated IL-1ß and the NLRP3 inflammasome in liver tissues in an effort to clarify their role in the pathophysiology of chronic viral hepatitis. METHODS: We studied liver biopsies from patients with a new diagnosis of either chronic hepatitis B (CHB) and chronic hepatitis C (CHC) or patients with chronic hepatitis B in remission (CHB-rem). The biopsies were separated in two parts. The first part was sent to histology to determine the grade of inflammation and fibrosis. From the second part, RNA was extracted and converted to cDNA used in semi-quantitative Real-Time PCR to measure the levels of IL1B, CASP1, NLRP3, ASC and IL1RA. The cell lines used in the in vitro experiments were Huh7.5, LX2 and THP-1 in variety of combinations of monocultures, co-cultures and triple cultures with one of the cell lines infected with the JFH-1 HCV clone. From the cell cultures RNA was extracted and converted to cDNA. For cell lines, we focused in the expression of IL1B and NLRP3. RESULTS: The expression of IL1B, CASP1 and NLRP3 were found significantly different between our groups (p = 0.001, p = 0.001 and p = 0.038, respectively). CHB patients displayed significantly higher IL1B and CASP1 mRNA levels compared to both CHB-rem and CHC patients. IL1B expression significantly correlates with liver biochemical data in CHB patients (AST: p = 0.006, r = 0.457; ALT p = 0.002, r = 0.497). Finally, mRNA levels of IL1B in CHB patients significantly correlate with the degree of inflammation (p = 0.016) but not the stage of fibrosis (p = 0.362). Interestingly, the relative expression of IL1B in triple culture experiments in vitro was below of 1.5-fold, suggesting no activation of IL1B. Moreover, no activation of NLRP3 was demonstrated in all investigated in vitro conditions. CONCLUSION: IL-1ß might play an important role in the pathogenesis of chronic hepatic inflammation from HBV, but not from HCV.

Serum Fas Ligand, Serum Myostatin and Urine TGF-ß1 Are Elevated in Autosomal Dominant Polycystic Kidney Disease Patients with Impaired and Preserved Renal Function.

BACKGROUND/AIMS: The pathophysiology of renal disease progression in autosomal dominant polycystic disease (ADPKD) is largely unknown. Recent evidence suggests microvascular dysfunction leading to renal ischemia, as an additional pathway for renal function decline. This study examined the levels of serum Fas ligand (FasL), serum myostatin and urine transforming growth factor-beta 1 (TGF-ß1) and their association with markers of endothelial dysfunction, in ADPKD patients with preserved or impaired renal function. METHODS: Seventy-eight participants were enrolled in the study, divided in three groups: Group A consisted of 26 ADPKD patients with impaired renal function (eGFR 45-70 ml/min/1.73m2), Group B of 26 ADPKD patients with preserved renal function (eGFR > 70 ml/min/1.73m2), and Group C of 26 age- and sex- matched controls with no history of renal disease. Serum FasL, myostatin and urine levels of TGF-ß1 were measured as biomarkers of vascular dysfunction, apoptosis and fibrosis with ELISA techniques. RESULTS: Group A patients had significantly higher levels of FasL (13.12±1.69 ng/mL), myostatin (4.62±0.59 ng/mL) and urine logTGF-ß1 (3.56±0.49 ng/24h) compared to Group B (9.6±1.28 ng/mL, 3.06±0.35, and 2.09±0.37, respectively, p< 0.001 for all comparisons) or controls (6.59±1.17 ng/mL, 2.18±0.45 ng/ml, and 1.58±0.21, respectively, p< 0.001 for all comparisons). Patients in Group B had also higher levels of all markers compared to controls (p< 0.001), despite having similar renal function. In ADKPD patients negative associations of eGFR with FasL (r=-0.799, p< 0.001), myostatin (r=-0.856, p< 0.001) and TGF-ß1 (r=-0.476, p< 0.001) but positive correlations of these markers with asymmetric dimethylarginine (ADMA) (r=0.825; r=0.749; and r=0.599, respectively p< 0.001) were noted. Multivariate analysis demonstrated that FasL was independently associated with high urine TGF-ß1 (OR 3.774, 95%CI 1.180-12.072, p=0.025). CONCLUSIONS: ADPKD patients with moderately preserved renal function have higher levels of FasL, myostatin and urine TGF-ß1 than controls. These results indicate that an interplay between endothelial dysfunction and renal ischemia with mechanisms linked to apoptosis and fibrosis may be present even in early stages of ADPKD.

Icodextrin-associated generalized exfoliative skin rash in a CAPD patient: a case-report.

BACKGROUND: Icodextrin is a starch-derived, water soluble glucose polymer, which is used as an alternative to glucose in order to enhance dialytic fluid removal in peritoneal dialysis patients. Although the safety and efficacy of icodextrin is well-established, its use in everyday clinical practice has been associated with the appearance of skin rashes and other related skin reactions. CASE PRESENTATION: Herein, we report the rare case of a 91-year-old woman with a history of severe congestive heart failure, who initiated continuous ambulatory peritoneal dialysis with icodextrin-based dialysate solutions and 15 days after the initial exposure to icodextrin developed a generalized maculopapular and exfoliative skin rash extending over the back, torso and extremities. Discontinuation of icodextrin and oral therapy with low-dose methyl-prednisolone with quick dose tapering improved the skin lesions within the following days. CONCLUSIONS: This case report highlights that skin hypersensitivity is a rare icodextrin-related adverse event that should be suspected in patients manifesting skin reactions typically within a few days or weeks after the initial exposure.

Accuracy of a Newly-Introduced Oscillometric Device for the Estimation of Arterial Stiffness Indices in Patients on Peritoneal Dialysis: A Preliminary Validation Study.

The aim of the present study was to compare the aortic systolic blood pressure (aSBP), heart-rate-adjusted augmentation index (AIx75), and pulse wave velocity (PWV) obtained using the Mobil-O-Graph (IEM, Stolberg, Germany) and SphygmoCor (AtCor, Sydney, Australia) devices in patients receiving peritoneal dialysis (PD).After a 10-minute rest in the supine position, the Mobil-O-Graph and SphygmoCor devices were applied in randomized order in 27 consecutive PD patients. The agreement between the measurements produced by the Mobil-O-Graph and SphygmoCor devices was explored using Bland-Altman analysis.The Mobil-O-Graph-derived aSBP, AIx75, and PWV did not differ from the same measurements obtained with SphygmoCor (aSBP: 120.5 ± 18.2 mmHg vs. 124.4 ± 19.0 mmHg, p = 0.438; AIx75: 27.0% ± 12.4% vs. 24.5% ± 10.6%, p = 0.428; PWV: 9.5 ± 2.1 m/s vs. 10.1 ± 3.1 m/s, p = 0.397). The slight difference in the estimation of aSBP is possibly explained by the difference in brachial SBP used for the calibration of the devices (131.0 ± 20.6 mmHg vs. 134.5 ± 19.7 mmHg, p = 0.525). Mobil-O-Graph-derived measurements correlated strongly with paired measurements obtained with the SphygmoCor device. Bland-Altman plots showed no evidence of asymmetry and a wide range of agreement between the two devices.Our study shows acceptable agreement between Mobil-O-Graph and SphygmoCor in the estimation of arterial stiffness indices in PD patients. Accordingly, the Mobil-O-Graph device accurately performs aortic ambulatory blood pressure monitoring in this population.