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Chronic inflammation and proteinuria is a risk factor for cardiovascular disease (CVD) in patients with chronic kidney diseases and rheumatologic disorders. Our aim was to investigate the CVD events (CVDEs) and survival between the patients with FMF-related AA amyloidosis and glomerulonephropathies (GN) to define possible predictors for CVDEs. A prospective follow-up study with FMF-amyloidosis and glomerulonephropathy (GN) was performed and patients were followed for CVDEs. Flow-mediated dilatation (FMD), FGF-23, serum lipid, hsCRP levels, BMI and HOMA were assessed. A Cox regression analysis was performed to evaluate the risk factors for CVDEs. There were 107 patients in the FMF-amyloidosis group and 126 patients with GN group. Forty-seven CVDEs were observed during the 4.2-years follow up; all 28 patients in the FMF-amyloidosis group and 14/19 patients with GN developed CVDEs before the age of 40 (p = 0.002). CVD mortality was 2.8 times higher (95% CI 1.02–7.76) in patients with FMF-amyloidosis. Across both groups, FMD and FGF23 (p

The aim of the study was to compare the clinical phenotype of patients with familial Mediterranean fever (FMF)-related AA amyloidosis, according to the age of FMF diagnosis and E148Q genotype. Patients with biopsy-confirmed FMF-related AA amyloidosis were included in the study. Tel-Hashomer criteria were applied in the diagnosis of FMF. All patients had detailed baseline assessment of clinical features, renal functions, genetic testing, histopathological diagnosis of amyloidosis, and treatment received. Multiple comparisons were performed according to the age of diagnosis, disease phenotype, mutation, and mortality. Our study included 169 patients with a diagnosis of AA amyloidosis. There were 101 patients diagnosed with FMF &lt, 18 years of age and 68 patients diagnosed who were ≥18 years of age. The three most common clinical manifestations were fever (84.6%), abdominal pain (71.6%), and arthritis (66.9%). The most common allele among FMF patients was M694V (60.6%), followed by E148Q (21.4%), and M680I (10.3%). The most frequent genotypes were M694V/M694V (45.0%), M694V/E148Q (14.8%), and E148Q/E148Q (11.2%) among 169 patients in our cohort. During the follow-up period, 15 patients (10 male, 5 female) died, of whom 14 had M694V homozygous genotype and one was homozygous for E148Q. Clinicians should be aware of patients with homozygous E148Q genotype for close monitoring and further evaluation. The possible relationship between E148Q and AA amyloidosis needs to be confirmed in other ethnicities.

Bu calismanin temel amaci, Konya bolgesindeki kara havuc ureten tarim isletmelerinin mekanizasyon seviyeleri icin bir veri tabani olusturmakti. Ornek koyler bilerek secildi ve yuz yuze anket yapmak icin 37 isletme ziyaret edildi. Mevcut bulgular isletme basina arazi buyuklugunun 1124,6 da, ortalama arsa sayisinin 10,2, toplam arsa sayisinin 379 ve ortalama arsa buyuklugunun 78,8 da oldugunu gostermistir. Toplam ekili alanlarin yaklasik% 62,69'u kara havuc uretiminde kullanilmistir ve bunu sirasiyla sulanan bugday tarimi (% 15,39), domates tarimi (% 7,09) ve sulu arpa tarimi (% 6,61) izlemistir. Mevcut isletmelerin mekanizasyon seviyelerine gore isletme basina traktor sayisi 2.81, ortalama traktor gucu 68.65 kW, traktor basina alet ve makine sayisi 6.52, -1 , 1 000 ha alan basina traktor sayisi 24,99 idi ve traktor basina ekili alan 40,01 ha olarak hesaplandi. Bu calismanin temel amaci, Konya bolgesindeki kara havuc ureten tarim isletmelerinin mekanizasyon seviyeleri icin bir veri tabani olusturmakti. Ornek koyler bilerek secildi ve yuz yuze anket yapmak icin 37 isletme ziyaret edildi. Mevcut bulgular isletme basina arazi buyuklugunun 1124,6 da, ortalama arsa sayisinin 10,2, toplam arsa sayisinin 379 ve ortalama arsa buyuklugunun 78,8 da oldugunu gostermistir. Toplam ekili alanlarin yaklasik% 62,69'u kara havuc uretiminde kullanilmistir ve bunu sirasiyla sulanan bugday tarimi (% 15,39), domates tarimi (% 7,09) ve sulu arpa tarimi (% 6,61) izlemistir. Mevcut isletmelerin mekanizasyon seviyelerine gore isletme basina traktor sayisi 2.81, ortalama traktor gucu 68.65 kW, traktor basina alet ve makine sayisi 6.52, -1 , 1 000 ha alan basina traktor sayisi 24,99 idi ve traktor basina ekili alan 40,01 ha olarak hesaplandi.

Background:While the pathophysiology of chronic disorders varies there are three basic mechanisms - inflammation, oxidative stress and endothelial dysfunction – that are common in many chronic diseases. These mechanisms, which have a dynamic structure, are key to homeostasis. However, the failure of these mechanisms to work synchronously can lead to morbidity complicating the course of many chronic diseases.Objectives:To evaluate the effect of anti-atherosclerotic liquid (AAL), anti-inflammatory capsules (AIC) and anti-oxidant liquid (AOL) supplementation on the flow-mediated dilatation (FMD), inflammatory, oxidative stress and endothelial dysfunction markers in patients with selected chronic diseasesMethods:We analyzed data of 178 patients from cohorts with selected chronic diseases (Rheumatoid arthritis, familial Mediterranean fever, DM type-2, Hypertension, Multiple sclerosis, Chronic obstructive pulmonary disease, Alzheimer disease and Cancer) in this quasi-experimental study. Endothelial dysfunction was determined by FMD and serum asymmetric dimethylarginine (ADMA) levels. Serum ADMA, high sensitive C-reactive protein (hs-CRP), serum PTX3, malondialdehyde (MDA), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), glutathione peroxidase (GSH-Px) levels and FMD were studied in baseline and after 12 weeks of Morinda citrifolia (AAL, 3 ml once per day), omega-3 (AIC, 3 capsules once per day) and extract with Alaskan blueberry and 21 different red purple fruit vegetables (AOL, 30 ml once per day). Stepwise multivariate regression analysis evaluated the association of FMD with clinical and serologic parameters.Results:Serum ADMA, MDA, PTX3, hsCRP and albumin levels, and proteinuria were significantly decreased and CuZn-SOD, GSH-Px and FMD levels were significantly increased following AAL, AIC and AOL therapies. FMD was negatively correlated with serum ADMA, MDA, PTX3, hsCRP levels, SBP and DBP and positively correlated to CuZn-SOD and eGFR levels both at baseline and after the 12-weeks treatment period. Multivariate regression analysis revealed that ADMA and PTX3 levels were independently related to FMD both before and after AAL, AIC and AOL therapies (Table 1, Figure 1).Conclusion:Our study shows that serum ADMA, MDA, PTX3 levels are associated with endothelial dysfunction in patients with selected chronic diseases. Short-term AAL, AIC and AOL therapies significantly improves FMD and normalizes ADMA, PTX3, hsCRP and MDA. This may have implications for adjunctive therapy in a number of chronic disorders.References:[1] Yilmaz MI, Saglam M, Caglar K, Cakir E, Sonmez A, Ozgurtas T et al. The determinants of endothelial dysfunction in CKD: oxidative stress and asymmetric dimethylarginine. Am J Kidney Dis. 2006;47(1):42-50. doi:10.1053/j.ajkd.2005.09.029.Disclosure of Interests:None declared

While the pathophysiology of chronic disorders varies there are three basic mechanisms - inflammation, oxidative stress and endothelial dysfunction – that are common in many chronic diseases. However, the failure of these mechanisms to work synchronously can lead to morbidity complicating the course of many chronic diseases. We analyzed data of 178 patients from cohorts with selected chronic diseases in this quasi-experimental study. Endothelial dysfunction was determined by flow-mediated dilatation (FMD) and asymmetric dimethylarginine (ADMA) levels. Serum ADMA, high sensitive C-reactive protein (hs-CRP), serum PTX3, malondialdehyde (MDA), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), glutathione peroxidase (GSH-Px) levels and FMD were studied in baseline and after 12 weeks of Morinda citrifolia (anti-atherosclerotic liquid- AAL), omega-3 (anti-inflammatory capsules- AIC) and extract with Alaskan blueberry (anti-oxidant liquid- AOL). Stepwise multivariate regression analysis was used to evaluate the association of FMD with clinical and serologic parameters. Serum ADMA, MDA, PTX3, hsCRP and albumin levels, and proteinuria were significantly decreased while CuZn-SOD, GSH-Px and FMD levels were significantly increased following AAL, AIC and AOL therapies. The FMD was negatively correlated with serum ADMA, MDA, PTX3, and hsCRP levels and positively correlated with CuZn-SOD and eGFR levels. ADMA and PTX3 levels were independently related to FMD both before and after AAL, AIC and AOL therapies. Our study shows that serum ADMA, MDA, PTX3 levels are associated with endothelial dysfunction in patients with selected chronic diseases. In addition, short-term AAL, AIC and AOL therapies significantly improves a number of parameters in our cohort and can normalize ADMA, PTX3, hsCRP and MDA levels.

Introduction: Patients with hypogonadism are at increased risk of cardiac and metabolic diseases and osteoporosis. Vitamin D and Fibroblast growth factor-23 (FGF-23) play role in the regulation of bone mineral metabolism and endothelial functions. Low vitamin D levels are reported in hypogonadism, while there is no data about the effect of testosterone replacement therapy (TRT). We investigated the effect of TRT on vitamin D and FGF-23 levels along with endothelial functions and insulin resistance in hypogonadal patients. Material and methods: Patients with congenital hypogonadotrophic hypogonadism (CHH) (n=32, age 20.6 ±1.58 years) were enrolled. TRT was implemented in transdermal form. The demographic parameters, FGF-23, 25(OH)D3, Asymmetric dimethylarginine (ADMA) and homeostatic model assessment of insulin resistance (HOMA-IR) levels were measured both before and after TRT. Results: After a follow-up period of 3.63±1.33 months, ADMA and FGF-23 levels were significantly increased (p=0.03 and p=0.005 respectively), while the 25(OH)D3 and HOMA-IR index were not significantly changed. The body mass index and waist circumference levels of the patients were also increased (p

Background:Amyloid A (AA) amyloidosis, previously known as secondary or reactive amyloidosis, is a long-recognized severe complication of some chronic inflammatory diseases. The pathogenesis and risk factors for amyloidosis in Familial Mediterranean Fever (FMF) remain partially understood (1). The development of AA amyloidosis is dependent on ethnicity and country of residence (2). In the pre-colchicine era, renal AA-amyloidosis was largely reported patients of Turkish (67%) and Sephardic Jewish ancestry (26.5%) (2,3). Currently it’s well known that the MEFV M694V variant associated with high risk of amyloidosis however, mutations on exon 2, specifically E148Q variant remained controversial.Objectives:To evaluate the E148Q mutation variant and concomitant AA Amyloidosis secondary to FMF after adjusted clinical-demographic characteristics.Methods:Patients were recruited from the renal unit at Epigenetic Health Center outpatient clinic in Turkey between September 2003 and February 2020. Patients who had biopsy confirmed FMF related AA amyloidosis were included the study. Tel-Hashomer criteria were applied in the diagnosis of FMF. The clinical characteristics of FMF patients and medication history were recorded by the physician at the time of registry entry. All patients had detailed baseline assessment of clinical features, renal functions, genetic testing, histopathological diagnosis of amyloidosis, and treatment received. We performed multiple comparisons according to the age of diagnosis, demographic features, disease phenotype, allele frequency, type of mutation and mortality. Statistical analysis was performed with Statistical Package of Social Science (SPSS) for Windows, version 15.0 (SPSS Inc, Chicago, IL).Results:Our registry consists of 195 patients with a diagnosis of AA amyloidosis. Complete information on 169 patients (lost to follow up, n=26) were included. The median age was 36 (19-49) years; male/female ratio was 1.6 (104/65). The median follow-up duration was 15.0 years (4-17 years). There were 101 patients diagnosed with FMF Conclusion:Patients with FMF related AA amyloidosis have an increased risk for mortality. This study confirmed the association between M694V and FMF-associated AA amyloidosis, which has been reported in many studies. Close clinical follow-up and further evaluation of patients with the E148Q mutation is warranted specifically if residing in FMF endemic areas. The possible relationship between E148Q and AA amyloidosis need to be confirmed in other cohorts.References:[1]Erer B, Demirkaya E, Ozen S, Kallinich T. What is the best acute phase reactant for familial Mediterranean fever follow-up and its role in the prediction of complications? A systematic review. Rheumatology international. 2016;36(4):483-7.[2]Touitou I, Sarkisian T, Medlej-Hashim M, Tunca M, Livneh A, Cattan D, et al. Country as the primary risk factor for renal amyloidosis in familial Mediterranean fever. Arthritis and rheumatism. 2007;56(5):1706-12.[3]Pras M, Bronshpigel N, Zemer D, Gafni J. Variable incidence of amyloidosis in familial Mediterranean fever among different ethnic groups. Johns Hopkins Med J. 1982;150(1):22-6.Disclosure of Interests:None declared

Background:Few studies have focused on Familial Mediterranean Fever (FMF)-related AA amyloidosis and cardiovascular disease event risk. Systemic inflammation stimulates the development and progression of atherosclerosis which is accelerated by vascular endothelial inflammation and enhanced oxidative stress. Excessive reactive oxygen species (ROS) generation has been reported in FMF, which correlated with attack severity. ROS may also be involved in amyloid formation, and in the pathogenesis of progressive renal injury.Objectives:In this non-randomized, 24 weeks open label interventional study, we aimed to evaluate the effect of a combination of natural products on parameters related to inflammation, endothelial dysfunction and oxidative stress in a cohort of FMF patients with AA amyloidosis.Methods:Morinda citrifolia (anti-atherosclerotic liquid- AAL), omega-3 (anti-inflammatory capsules- AIC) and extract with Alaskan blueberry (anti-oxidant liquid- AOL) were given to patients with FMF related AA amyloidosis. We included patients with biopsy proven AA amyloidosis, older than 18 years who have normal estimated glomerular filtration rate (eGFR) and proteinuria [>3500mg/day]. Flow-mediated dilatation (FMD), asymmetric dimethylarginine (ADMA), hs-CRP, serum PTX3, Carotis intima media thickness (CIMT), malondialdehyde (MDA), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), glutathione peroxidase (GSH-Px) levels were studied in baseline and after 24 weeks.Results:67 FMF-related amyloidosis [52 male (77.6%); median recruitment age 36 years (range 21-66)] were enrolled. M694V mutation was the most common mutation found (74%), with 50.7% of the patients in homozygosity. All patients were treated with colchicine, and most of them (83.6%) has been on colchicine treatment at the time of enrollment. Serum ADMA, MDA, PTX3, hsCRP, cholesterol, and proteinuria were significantly decreased compared to baseline, while CuZn-SOD, GSH-Px and FMD levels were significantly increased following AAL, AIC and AOL therapies (Table 1). The change of the inflammatory markers PTX3, and hsCRP were negatively correlated with the change in FMD and positively correlated with the change of proteinuria, ADMA, MDA, cholesterol and CIMT.Conclusion:24 weeks of AAL, AIC and AOL combined supplementation was significantly associated with reduction in serum inflammatory markers (PTX3 and hsCRP), improved endothelial functions (FMD, ADMA), and oxidative state (MDA). Our findings highlight the link among the three pathogenetic mechanisms including inflammation, endothelial function and oxidative status in progression of atherosclerosis and renal injury in patients with FMF related AA amyloidosis. Efficient control of these three mechanisms can have long term benefits from the cardiovascular and renal perspective of the patients with AA amyloidosis.References:[1]Romano M et al. Sci Rep, 2020[2]Yilmaz M et al. Sci Rep, 2020Table 1.Comparison of clinical and laboratory characteristics at the baseline and after 24 weeks of AAL, AIC and AOL supplementationBaselineMean (SD)24th weekMean (SD)DeltaMean (SD)pTotal Cholesterol (mg/dl)221.2 (60.3)155.8 (35.4**)-65.3 (55.5)eGFR (ml/min/ 1.73 m2)110.2 (12.8)104.1 (11.2**)-6.1 (11.9)Malondialdehyde (MDA) (nmol/ml)4.2 (1.8)1.8 (0.5**)-2.2 (1.8)CuZn-SOD (U/ml)431.5 (154.7)538.1 (146.4**)159.7 (211.8)GSH-Px (U/ml)47.8 (13.2)74.1 (20.3**)26.3 (21.1)ADMA (µmol/l)4.5 (2.6)1.3 (0.6**)-3.2 (2.5)FMD (%)5.0 (0.7)6.4 (0.8**)1.3 (0.9)CIMT (mm)0.9 (0.2)0.7 (0.1)-0.2 (0.2)Proteinuria (mg/24h)6855.3 (3116.9)4079.9 (2359.6)-2775.3 (2874.5)hs-CRP (mg/l)25.5 (4.4-48.0)3.0 (1.0-9.1)*-20.8 (11.2)PTX3 (ng/ml)13.4 (2.3-67.0)2.3 (0.4-14.5)*-17.5(17.5)Disclosure of Interests:None declared

Introduction Increasing evidence suggests that inflammation and increased macrophage activity have a central role in pathogenesis of atherosclerosis. It is shown that chitotriosidase (CHIT-1) is a marker of macrophage activity in atherosclerotic plaque, and is found associated with severity of atherosclerotic lesion. There is no data about CHIT-1 activity of hemodialysis patients in the literature. Thus, we hypothesized that in hemodialysis patients, CHIT-1 levels might be a novel biomarker in early atherosclerosis. Methods Forty-five hemodialysis patients were included in the study (age: 61.93 ± 13.34). Intima media thickness (IMT) was evaluated with high-resolution B-mode ultrasonography. Biomarker levels were measured in serum of patients. Findings We found positive correlation among IMT, age (R: 0.426, P: 0.004) and, CHIT-1 value (R: 0.462, P: 0.001) in spearman correlation analysis. When age, CRP, creatinine, P, Alb, CHIT-1 were chosen as measures that can effect IMT in multiple regression model, IMT level was related with CHIT-1 (Beta: 0,396, P: 0.012) and age (Beta: 0,313 P: 0,048) independently. Discussion In conclusion, this is the first report showing that serum CHIT-1 level was related independently with carotid IMT in hemodialysis patients. This biomarker might have an unknown role in the development of atherosclerosis during uremia.

Obesity increases hepatocellular carcinoma (HCC) risks via unknown mediators. We report that hepatic unconventional prefoldin RPB5 interactor (URI) couples nutrient surpluses to inflammation and non-alcoholic steatohepatitis (NASH), a common cause of HCC. URI-induced DNA damage in hepatocytes triggers inflammation via T helper 17 (Th17) lymphocytes and interleukin 17A (IL-17A). This induces white adipose tissue neutrophil infiltration mediating insulin resistance (IR) and fatty acid release, stored in liver as triglycerides, causing NASH. NASH and subsequently HCC are prevented by pharmacological suppression of Th17 cell differentiation, IL-17A blocking antibodies, and genetic ablation of the IL-17A receptor in myeloid cells. Human hepatitis, fatty liver, and viral hepatitis-associated HCC exhibit increased IL-17A correlating positively with steatosis. IL-17A blockers may prevent IR, NASH, and HCC in high-risk patients.

Abnormalities of thyroid function are commonly seen in chronic kidney disease (CKD) patients. They are associated with adverse clinical conditions such as atherosclerosis, endothelial dysfunction, inflammation and abnormal blood pressure variability. We investigated the association between thyroid disorders and endothelial function, assessed by flow-mediated dilatation (FMD) and carotid intima-media thickness (CIMT), and cardiovascular events (CVE) in CKD patients. This observational cohort study included 305 CKD (stages 1–5) patients. Routine biochemistry, including free T3, free T4 and thyroid stimulating hormone, fibroblast growth factor-23 (FGF-23) and FMD, CIMT were measured. We divided patients into four groups according to thyroid hormone status: euthyroidism, subclinical hyperthyroidism, subclinical hypothyroidism, and euthyroid sick syndrome. Fatal and composite CVE were recorded for a median 29 months. Patients with subclinical hypothyroidism had a higher prevalence of hypertension and diabetes and also were more likely to have higher values of systolic CIMT, phosphorus, intact parathormone (iPTH), FGF-23, homeostasis model assessment-insulin resistance and lower levels of FMD than euthyroid patients. In the unadjusted survival analysis, subclinical hypothyroidism and euthyroid sick syndrome were associated with an increased risk for the outcome as compared with euthyroidism [hazard ratio 30.63 (95 % confidence interval 12.27–76.48) and 12.17 (3.70–39.98), respectively]. The effects of subclinical hypothyroidism and euthyroid sick syndrome were maintained even in fully adjusted models. We demonstrated that subclinical hypothyroidism and euthyroid sick syndrome are associated with increased CVE in CKD patients. Further studies are needed to explore these issues.

Vascular injury and dysfunction contribute to cardiovascular disease, the leading cause of death in patients with chronic kidney disease (CKD). Osteoprotegerin (OPG) is a soluble member of the tumor necrosis factor receptor superfamily that has been linked to atherogenesis and endothelial dysfunction. Elevated circulating OPG levels predict future cardiovascular events (CVE). Our aim was to evaluate the determinants of circulating OPG levels, to investigate the relationship between OPG and markers of vascular damage and to test whether OPG improves risk stratification for future CVE beyond traditional and renal-specific risk factors in a CKD population. 291 patients with CKD stage 1-5 not on dialysis were included in the study. In the multivariate analysis, OPG was a significant predictor for flow-mediated dilatation, but not for carotid intima media thickness levels. During follow-up (median 36 months, IQR = 32-42 months), 87 patients had CVE. In the Cox survival analysis, OPG levels were independently associated with CVE even after adjustment for traditional and renal-specific cardiovascular risk factors. The addition of OPG to a model based on commonly used cardiovascular factors significantly improved the reclassification abilities of the model for predicting CVE. We show for the first time that OPG improves risk stratification for CVE in a non-dialysis CKD population, above and beyond a model with established traditional and renal-specific cardiovascular risk factors, including estimated glomerular filtration rate and fibroblast growth factor 23.

Both elevated serum uric acid and serum asymmetric dimethylarginine (ADMA) are risk factors for cardiovascular disease. We hypothesized that combined elevation of uric acid and ADMA amplifies the risk of all-cause mortality and/or cardiovascular events (CVE) in patients with chronic kidney disease (CKD).A total of 259 patients with CKD stages 1-5 were followed up in a time-to-event analysis for all-cause mortality and fatal and non-fatal CVE (including death, stroke, and myocardial infarction). Baseline measurements included serum uric acid and ADMA and endothelial function [ultrasound determined flow-mediated dilatation (FMD)].As a measure of endothelial function, log FMD value was positively associated with log eGFR, but negatively associated with log ADMA and log uric acid levels. During follow-up (median 38 months), 24 (9.3 %) deaths, 90 (34.7 %) CVE, and 95 (36.7 %) deaths and CVE (composite outcome) occurred. In the univariate Cox analysis, patients with both serum uric acid and ADMA levels above the median had an increased risk of all-cause mortality, CVE, and the composite outcome (HR 5.06, 95 % CI 2.01-12.76; HR 4.75, 95 % CI 2.98-7.59; and HR 4.13, 95 % CI 2.66-6.43, respectively). However, after adjustment for renal-specific risk factors (glomerular filtration rate, proteinuria, and hsCRP), this association was maintained only for CVE and the composite outcome. The addition of both biomarkers into a model with traditional and renal-specific risk factors did not increase the prediction abilities of the model for none of the three outcomes.Elevated serum uric acid and ADMA levels are associated with an increased cardiovascular risk, but their combination does not improve risk prediction. The effects are not additive, possibly because uric acid may lie in the causal pathway by which ADMA acts.

WOS: 000392937800028 PubMed ID: 28006774 Background/Aims: Fabry disease is a treatable cause of chronic kidney disease (CKD) characterized by a genetic deficiency of a-galactosidase A. European Renal Best Practice (ERBP) recommends screening for Fabry disease in CKD patients. However, this is based on expert opinion and there are no reports of the prevalence of Fabry disease in stage 1-5 CKD. Hence, we investigated the prevalence of Fabry disease in CKD patients not receiving renal replacement therapy. Methods: This prospective study assessed a-galactosidase activity in dried blood spots in 313 stage 1-5 CKD patients, 167 males, between ages of 18-70 years whose etiology of CKD was unknown and were not receiving renal replacement therapy. The diagnosis was confirmed by GLA gene mutation analysis. Results: Three (all males) of 313 CKD patients (0.95%) were diagnosed of Fabry disease, for a prevalence in males of 1.80%. Family screening identified 8 aditional Fabry patients with CKD. Of a total of 11 Fabry patients, 7 were male and started enzyme replacement therapy and 4 were female. The most frequent manifestations in male patients were fatigue (100%), tinnitus, vertigo, acroparesthesia, hypohidrosis, cornea verticillata and angiokeratoma (all 85%), heat intolerance (71%), and abdominal pain (57%). The most frequent manifestations in female patients were fatigue and cornea verticillata (50%), and tinnitus, vertigo and angiokeratoma (25%). Three patients had severe episodic abdominal pain attacks and proteinuria, and were misdiagnosed as familial Mediterranean fever. Conclusions: The prevalence of Fa bry disease in selected CKD patients is in the range found among renal replacement therapy patients, but the disease is diagnosed at an earlier, treatable stage. These data support the ERBP recommendation to screen for Fabry disease in patients with CKD of unknown origin. (C) 2016 The Author(s) Published by S. Karger AG, Basel Sanofi Genzyme Corporation; Intensificacion ISCIII and REDINREN [RD012/0021] We are indebted to our patients and their families for volunteering to contribute their medical information to the physicians who are dedicated to their care. This work was supported by grants from Sanofi Genzyme Corporation. The lead investigator had full access to all data in the study. All investigators take responsibility for the accuracy of the individual data that they entered in the system provided by FMF Arthritis Vasculitis and Orphan disease Research (FAVOR). AO was supported by Intensificacion ISCIII and REDINREN RD012/0021.

Neutrophil gelatinase-associated lipocalin (NGAL) is a member of the lipocalin family best known as a novel and early marker of acute kidney injury (AKI). Recent data suggest that NGQueryAL is not only a marker of AKI, but also an important player in the vascular remodeling, atherosclerotic plaque stability and thrombus formation. We conducted this study to investigate the association of serum NGAL levels with fatal and composite (fatal and non-fatal) cardiovascular events (CVE) in a cohort of patients with stage 1–5 CKD. This was an observational cohort study in which serum NGAL was obtained from 298 CKD (stages 1–5) patients. Fatal and composite CVE were recorded for a median 41 months. We examined alteration of serum NGAL through CKD groups as well as association with inflammatory markers. We also performed a Cox regression analysis to determine the association of NGAL with predefined clinical outcomes. The median value of NGAL was 50.5 ng/mL (IR 47.6–54.9 ng/mL), and higher NGAL values were recorded in diabetic patients. In a multiple linear regression model, including all univariate associates of NGAL, only log eGFR, log hs-CRP and log HDL cholesterol maintained an independent association with log NGAL. During the observational period, 30 patients died due to cardiovascular causes and 69 non-fatal CVE were registered. In the fully adjusted model, we observed a 2.08-fold increase in the risk of fatal CVE and a 1.50-fold increase in the risk of fatal and non-fatal CVE for each increment of 1 SD in log NGAL values. This is the first study that shows that serum NGAL is associated with cardiovascular events (fatal and non-fatal) in patients with CKD, independently of traditional risk factors, renal function and inflammation.

RESULTS: The mean age of the 104 patients was 60.03±17.01 years and the mean of dialysis vintage was 4.53±3.04 years. Of these patients, 62.5% declared their willingness to undergo KT, and among these, 76.9% declared that they had knowledge about KT. In regard to choice of donor, 79.7% stated that it was not important, while 56.7% were not informed about the existence of a waiting list for cadaveric donors.

The role of reversibility of nontraditional risk factors, like inflammation and CKD-mineral bone disorder, in the reduction of cardiovascular risk after renal transplantation is still scarcely defined.The longitudinal relationship between C-reactive protein, CKD-mineral bone disorder biomarkers, and intima media thickness was investigated in a series of 178 patients (age=32±10 years) with stage 5 CKD maintained on chronic dialysis who underwent echo-color Doppler studies of the carotid arteries before and after renal transplantation. Smokers and patients with diabetes were excluded from the study. In all patients, immunosuppression was performed by a standard regimen on the basis of calcineurin inhibitors. Healthy controls were specifically selected to match the age and sex distribution of the patients. Biochemical and intima media thickness assessments were repeated 6 months after transplantation.Before transplantation, intima media thickness in patients with stage 5 CKD on dialysis (average=0.9±0.2 mm) was higher (P0.001) than in well matched healthy controls (0.6±0.1 mm) and reduced substantially (-22%; 95% confidence interval, -24% to -20%) after transplantation (P=0.001). GFR (multivariable-adjusted β=0.23; P0.001), C-reactive protein (β=0.15; P0.001), and fibroblast growth factor 23 (β=0.28; P0.001) were the strongest independent correlates of intima media thickness before transplantation. Similarly, longitudinal changes in the same biomarkers were the sole independent correlates of simultaneous changes in intima media thickness (C-reactive protein: β=0.25; fibroblast growth factor 23: β=0.26; P0.001 for both) after renal transplantation. The evolution of intima media thickness after transplantation was largely independent of classic risk factors, including BP, LDL cholesterol, and insulin resistance, as measured by homeostatic model assessment.Intima media thickness improves after renal transplantation. Such an improvement associates with parallel changes in serum C-reactive protein and fibroblast growth factor 23. These observations are in keeping with the hypothesis that the decline in cardiovascular risk after transplantation, in part, depends on partial resolution of nontraditional cardiovascular risk factors, like inflammation and CKD-mineral bone disorder.

Rationale, aims and objectives Hypertension (HT) is prevalent in Turkey and even with pharmacological interventions HT control rates do not meet guideline recommendations. We aimed to estimate the proportion of hypertensive patients who achieved target blood pressure (BP) and seek to determine the predictors responsible for failure of to reach goals. Methods We conducted a retrospective cohort study involving patients with HT. A total of 437 patients were identified with a current diagnosis of HT at baseline. All available predictors for BP improvements were included in the multivariate linear regression model. Results Follow-up data on HT goal achievements was available for 276 (63.1%) participants. Only 18.1% of the patients at the baseline visit, and 48.6% at the follow-up visit achieved the overall SBP/DBP targets specified by the JNC-8 guideline. Significant differences were determined by baseline and 1st visit measurements of mean SBP/DBP levels (P

Patients with hypogonadism have poor cardiovascular and metabolic outcomes, and the effect of testosterone replacement therapy (TRT) is not clear. We investigated the presence of inflammation, insulin resistance and endothelial dysfunction in an unconfounded population of congenital hypogonadotrophic hypogonadism (CHH) and the effect of TRT on these subjects. A total of 60 patients with CHH (mean age 21.82±2.22 years) and 70 healthy control subjects (mean age 21.32±1.13 years) were enrolled. The demographic parameters, Asymmetric dimethylarginine (ADMA), TNF-like weak inducer of apoptosis (TWEAK), high sensitive C reactive protein (hs-CRP) and homeostatic model assessment of insulin resistance (HOMA-IR) levels were measured before and after TRT. The patients had higher Waist Circumferences (WC) (p=0.009), Diastolic Blood Pressures (p=0.02), Triglycerides (p=0.03), ADMA, insulin and HOMA-IR levels (p

Background: Atrial electromechanical delay (AEMD) times were considered independent predictors of cardiovascular morbidity among the general population. We aimed at evaluating AEMD times and other risk factors associated with 2-year combined cardiovascular (CV) events in HD patients. Material and Methods: Sixty hemodialysis (HD) and 44 healthy individuals were enrolled in this prospective study. Echocardiography was performed before the mid-week dialysis session for HD patients. Data were expressed as mean ± SD. Spearman test was used to assess linear associations. Survival was examined with the Kaplan-Meier method. Multivariate Cox regression analysis was used to determine the predictors of combined CV events in this cohort. Results: At the beginning of the study, left intra-atrial-AEMD times were significantly longer in HD patients compared to the left intra-atrial-AEMD times in healthy individuals. After 24 months, 41 patients were still on HD treatment and 19 (31.6%) had died. Serum triglyceride, total cholesterol and albumin were found to be higher and C-reactive protein (CRP) levels, left intra-atrial EMD time (LIAT) and interatrial EMD times were found to be lower in survived HD patients. With the cut-off median values of 3.5 g/dl for albumin, 0.87 mg/dl for CRP, 157 mg/dl for total cholesterol and 151 mg/dl for triglyceride, the Kaplan-Meier curves demonstrated significant differences in terms of all-cause mortality. We also demonstrated the Kaplan-Meier survival curves of HD patients according to tertile values of LIAT. Cox regression analysis revealed that increased CRP and higher LIAT were found to be independent predictors of combined CV events. Conclusions: Increased LIAT and inflammation were found to be closely associated with 2 years combined CV events and all-cause mortality in HD patients.

Cardiovascular events make up the primary cause of death in hemodialysis patients, and the risk for cardiovascular mortality is significantly increased by vascular calcification, a condition observed frequently in this patient population. The mechanisms underlying the pathogenesis of vascular calcification are complex, and many factors facilitate or hinder the development of calcification. In this review, we first summarize the main factors contributing to the pathogenesis of vascular calcification in patients with end-stage renal disease. We then explore the role of calcification inhibitors in the calcification process, as well as their effect on vascular dysfunction and mortality in hemodialysis patients.

Illuminating intestine irradiation High-dose radiation exposure affects multiple body systems, including the blood and the neurovascular system. Radiation can also cause severe intestinal toxicity, known as gastrointestinal syndrome (GIS). Working in mice, Chaves-Pérez et al. focused on the mechanisms underlying GIS. The molecular chaperone URI (unconventional prefoldin RPB5 interactor) labeled slow-cycling label-retaining (LR) cells, which are essential for organ regeneration following ionizing radiation. Reduced URI levels rendered LR cells highly proliferative via the activation of the β-catenin/c-MYC axis. Consequently, LR cells became radiosensitive, increasing GIS severity. Thus, URI protects LR cells to promote tissue regeneration in response to high-dose irradiation. Science , this issue p. eaaq1165

Background Profilin-1 is a ubiquitous, actin-binding protein that plays an important role in the regulation of actin polymerization and cytoskeleton remodeling thus contribute vascular dysfunction.We conducted this study to investigate the association of serum profilin-1 levels with fatal and non-fatal CVE in a cohort of patients with stage 1-5 CKD. Matherials and methods Serum concentrations of profilin-1 levels were determined by enzyme-linked immunosorbent assay. Endothelium-dependent vasodilatation (flow-mediated dilatation (FMD) and endothelium-independent vasodilatation (nitroglycerine mediated dilatation (NMD) of the brachial artery were assessed non-invasively, using high-resolution ultrasound. Results Both fatal and non-fatal CVE was significantly higher in patients with high profilin-1 levels. Kaplan–Meier survival curves showed that patients with profilin-1 below the median value (114 pg/ml) had higher cumulative survival compared with patients who had profilin-1 levels above the median value (log-rank test, P

Patients with end-stage renal disease undergoing dialysis commonly experience derangements in the hypothalamic-pituitary-gonadal axis together with alterations at the level of synthesis and clearance of many hormones. This hormonal imbalance, even if asymptomatic, has recently been associated with increased mortality in these patients. In this review, we summarize observational and mechanistic evidence linking hormonal alterations at the level of the thyroid and sex-hormone systems with this mortality risks.

The chronic kidney disease (CKD)-mineral and bone disorder (MBD) syndrome is an important contributor to the CKD-associated cardiovascular disease and high mortality rates. Sclerostin, a protein synthesized in osteocytes, is a potent downregulator of bone metabolism and a novel candidate for the bone-vascular axis in CKD patients. We tested whether serum sclerostin values are predictive for all-cause mortality and cardiovascular events (CVEs) in a CKD population.Serum sclerostin was obtained from 173 CKD (stage 3-5) and 47 control patients, and its concentration was correlated with estimated glomerular filtration rate and to mineral and vascular abnormalities that are present in the CKD evolution. All-cause mortality and CVEs were also analyzed in relation to serum sclerostin values.Patients with CKD showed higher sclerostin levels (median 63.5 pmol/L vs 52 pmol/L, P.001) than controls, with values progressively higher across the CKD stages. In univariate analysis, serum sclerostin concentrations were correlated with gender, estimated glomerular filtration rate, flow-mediated dilatation, and endothelium-independent vasodilatation as markers of endothelial dysfunction and with different serum CKD-MBD-associated parameters. However, in multivariate analysis, only gender, fibroblast growth factor-23, phosphate, flow-mediated dilatation, and cholesterol remained significantly associated with sclerostin levels. During the observational period, there were 19 deaths and 50 CVEs. In survival analysis, different sclerostin levels were associated with all-cause mortality and CVEs in these patients.This is the first study that shows that serum sclerostin values are associated, even after multiple adjustments, with fatal and nonfatal CVEs in a nondialyzed CKD population.

To determine the relationships between inflammatory mediators, mitral annular calcification (MAC), and osteocalcin in patients with chronic kidney disease (CKD).Echocardiographic data for 60 patients diagnosed as CKD were retrospectively evaluated. The patients were divided into 2 groups; patients with MAC (MAC+ group) and patients without MAC (MAC- group). The relationships between biochemical markers-including osteocalcin-and MAC were evaluated.The study included 19 female and 41 male patients. In all, 29 patients were MAC+ and 31 were MAC-. High-sensitive C-reactive protein (hsCRP) and osteocalcin levels were significantly higher in the MAC+ group (p 0.05). The eGFR was lower, serum calcitonin (we could not obtain calcitonin data for 15 patients), Ca, PO4, CaxPO4, the erythrocyte sedimentation rate, red cell distribution width, the neutrophil/Lymphocyte rate, and PTH were higher in the MAC+ group; however, the differences between the groups were not significant (p 0.05). The mitral E/A ratio, mitral peak Ea velocity, tricuspid E/A ratio, hsCRP, and the osteocalcin level were strongly correlated with MAC. Multivariate logistic regression analysis showed that only the osteocalcin level and mitral E/A ratio were independent variables, each with an independent effect on MAC.CKD patients in the MAC+ group had higher osteocalcin levels than those in the MAC- group, and left ventricular diastolic dysfunction was more common in the MAC+ group.

ObJEcTIVE: A number of studies report CXCL-16 as a new chemokine that mediates the collection of leukocytes and adhesion of macrophages to coronary artery smooth muscle cells, and stimulates atherosclerosis. However, there is a limited number of studies evaluating the levels of CXCL-16 in patients with Chronic Kidney Disease (CKD). We aimed to determine the serum level of CXCL-16 in patients with CKD and to clarify the relationship between CXCL-16 and hsCRP and glomerular filtration. MATERIAL and METHODs: Two hundred and twenty two patients with CKD were included in the study. The patients were divided into 3 groups according to the glomerular filtration rate (GFR) in accordance with the K/DOQI guideline. Patients with primary glomerulonephritis or tubulointerstitial nephritis, heart failure, or hepatic disease, patients who used immunosuppressive or cytotoxic drugs and renin-angiotensin system blockers were excluded from the study. REsULTs: There was a positive correlation between the grade of renal failure and CXCL-16 levels and a negative correlation between the GFR and CXCL-16 levels ( p

Objectives. Secondary amyloidosis is the most important complication of FMF and endothelial function is more severely impaired. Elevated asymmetric dimethyl arginine (ADMA) may mediate the excess cardiovascular disease (CVD) risk of this group. We aimed to compare endothelial function characteristics, including ADMA, in patients with FMF-related amyloidosis and primary glomerulopathies and to define risk factors for a CVD event. Methods. We undertook a cross-sectional study with prospective follow-up including consecutive patients with FMF-related amyloidosis (n = 98) or other non-diabetic glomerulopathies (n = 102). All patients had nephrotic-range proteinuria and normal glomerular filtration rate. Flow-mediated dilatation (FMD) was assessed and ADMA levels, CRP and pentraxin 3 (PTX3) were determined. Patients were followed for cardiovascular events. Results. Amyloidosis patients secondary to FMF showed higher levels of ADMA, CRP and PTX3 and lower FMD as compared with patients with other glomerulopathies. Cardiovascular events (n = 54) were registered during 3 years of follow-up. Increased ADMA levels and lower FMD were observed in patients with cardiovascular risk in both groups, but especially in individuals with amyloidosis. Conclusion. Patients with FMF-related amyloidosis have increased CVD event risk, probably related to the high ADMA levels, elevated inflammatory markers and decreased FMD measures observed in these patients.

Introduction and Aims: Serum p-cresyl sulfate associates with cardiovascular disease in patients at different stages of chronic kidney disease. p-Cresyl sulfate concentrations are determined by intestinal uptake of p-cresol, human metabolism to p-cresyl sulfate and renal clearance. Whether intestinal uptake of p-cresol itself is associated with cardiovascular disease in patients with renal disease has not been studied to date. Methods: We performed a prospective study in patients with chronic kidney disease stage 1-5 (clinicaltrials.gov NCT00441623). Intestinal uptake of p-cresol, under steady state conditions, was estimated from 24h urinary excretion of p-cresyl sulfate. Primary endpoint was time to first cardiovascular event, i.e. cardiac death, myocardial infarction/ischemia, ventricular arythmia, cardiovascular surgery, cerebrovascular accident or symptomatic peripheral arterial disease. Statistical analysis was done using Kaplan Meier estimates and Cox proportional hazard analyses. Results: In a cohort of 200 patients, median 24h urinary excretion of p-cresyl sulfate was 457.47 µmol (IQR 252.68-697.17). After a median follow-up of 52 months, 25 patients reached the primary endpoint (tertile 1/2/3: 5/6/14 events, log rank P 0.0368, see figure). Higher urinary excretion of p-cresyl sulfate was related with cardiovascular events (univariate hazard ratio per 100 µmol increase: 1.112, P 0.0015). In multivariate analysis, urinary excretion of p-cresyl sulfate remained a predictor of cardiovascular events, independent of markers of renal function (Hazard ratio 1.120, P 0.0022) and in different models with other cardiovascular risk factors (Framingham risk factors, cardiovascular history, diabetes mellitus and biochemical parameters). The independent association between urinary excretion of p-cresyl sulfate and outcome persisted after correction for serum p-cresyl sulfate. Conclusions: Intestinal uptake of p-cresol associates with cardiovascular disease independent of renal function. Insights into mechanisms governing intestinal generation and absorption of p-cresol may lead to identification of novel therapeutic targets to reduce cardiovascular disease risk in patients with chronic kidney disease.

Background Red cell distribution width (RDW) is a measure of erythrocyte size variability and has been shown as an independent predictor of mortality. The aim of this article was to evaluate the association of RDW with endothelial dysfunction in patients with chronic kidney disease (CKD). Methods Patients with 1 to 5 stages of CKD were included in the study. Endothelial function was assessed with flow-mediated dilatation (FMD). Estimated glomerular filtration rate (eGFR) and carotid intima media thickness (CIMT) were determined. Clinicode-mographic characteristics, biochemical values, complete blood counts, ferritin, C-reactive protein (CRP) and cholesterol levels were recorded. Spearman's correlation was used to determine correlates of RDW. Multivariate linear regression model was used to assess independent associates of FMD. Results Overall, 367 patients with CKD 1 to 5 were included in the study. RDW showed a significant increase from stage 1 to stage 5 CKD. Median RDW was 13.5. Patients with RDW values higher than median had significantly lower hemoglobin, eGFR and FMD values and higher CIMT and CRP values compared with patients who had RDW values below median. RDW showed a significant positive correlation with the presence of diabetes mellitus, CIMT and CRP, whereas a significant negative correlation with eGFR, ferritin and FMD. Multivariate analysis showed independent predictors of FMD as RDW, presence of diabetes, hemoglobin, eGFR, CRP, and serum albumin. Conclusions Multivariate regression model revealed RDW as a significant predictor of FMD independent of major confounding factors, such as diabetes, inflammation, anemia and kidney function in CKD.

Background/Aims: Ramipril attenuates renal Fibroblast growth factor-23 (FGF-23) expression, ameliorates proteinuria and normalizes serum phosphate in the diabetic Zucker rat with progressive renal disease suggesting that the renoprotective effect by this drug may be in part due to a FGF-23-lowering effect of angiotensin-converting enzyme (ACE) inhibition. Methods: In this nonrandomized study, we tested whether ACE-inhibition reduces circulating FGF-23 in type-2 diabetics with stage-1 chronic kidney disease (CKD) and proteinuria. Intact FGF-23, the eGFR, proteinuria and the endothelium-dependent flow-mediated (FMD) response to ischemia and other parameters were measured at baseline and after 12-weeks of treatment with ramipril (n = 68) or amlodipine (n = 32). Results: Blood Pressure (BP) fell to a similar extent (p < 0.001) in the two groups. However, 24 h proteinuria and the FMD improved more (both p < 0.01) in ramipril-treated patients than in amlodipine-treated patients. Changes in proteinuria (r = 0.47) and in FMD (r = -0.49) by ramipril were closely associated (p < 0.001) with simultaneous changes in FGF-23 and this link was confirmed in multiple regression analyses. In these analyses, the relationship between FMD and proteinuria changes attained statistical significance (p < 0.01) only in a model excluding FGF-23 suggesting that endothelial dysfunction and FGF-23 share a common pathway conducive to renal damage. Conclusion: Findings in this study contribute to generate the hypothesis that FGF-23 may be implicated in proteinuria and in endothelial dysfunction in diabetic nephropathy (clinicaltrials.gov (NCT01738945)).

Aim: Mean corpuscular volume (MCV) is a measure of size of red blood cells. Recently a few studies showed an association of macrocytosis with all-cause mortality. We aimed to assess the relationship of MCV with cardiovascular (CV) morbidity and mortality in patients with chronic kidney disease (CKD), and the effect of MCV on endothelial function. Methods: This is an observational cohort study with a prospectively maintained cohort of patients with stage 1–5 CKD. Estimated glomerular filtration rate (eGFR), flow mediated dilatation (FMD) and laboratory values were measured at baseline. Multivariate linear and Cox regression analyses were used to predict independent associations of FMD and composite CV events, respectively. Results: A total of 309 patients were included in the study. In contrast to anaemia MCV did not show a significant change among CKD groups. MCV was an independent predictor of FMD in addition to serum haemoglobin, CRP, diabetes, systolic blood pressure (SBP) and eGFR. Median MCV value was 85 fl. Kaplan–Meier analysis showed that at 38 months the survival rate was 97.6% in the group with MCV < 85 compared to 81.6% in the arm with MCV ≥ 85 (P < 0.001, log-rank test). Cox regression analysis showed MCV as a predictor of composite CV events independent of major confounding factors. Conclusion: This is the first study in the literature showing an independent association of MCV and FMD. Our results also determined MCV as an independent predictor of composite CV events independent of anaemia, inflammation, diabetes and eGFR in patients with CKD.

Background Soluble TWEAK (sTWEAK) and asymmetric dimethyl arginine (ADMA) concentrations have been associated with endothelial function in patients with chronic kidney disease (CKD). We tested the hypothesis that the improvement in endothelial function observed after renal transplantation is directly linked to the normalization of both sTWEAK and ADMA. Materials and methods One hundred and seventy-five kidney transplant recipients (71% men; 31·6 ± 9·4 years) were studied immediately before and on the 180th day post-transplantation. At each visit, blood samples were taken to assess circulating levels of sTWEAK and ADMA. Brachial artery endothelium-dependent vasodilatation (FMD) assessments were also performed. Results Renal transplantation was followed by an improvement in FMD. This improvement was paralleled by an increase in sTWEAK and a reduction in ADMA after transplantation (P

High FGF23 predicts renal function loss in chronic kidney disease (CKD) patients and graft failure in transplant patients. FGF23, parathyroid hormone and serum phosphate are all interrelated but among these CKD-MBD biomarkers only FGF23 is independently related with CKD progression. High FGF23 associates with endothelial dysfunction in CKD patients and in elderly individuals in the general population. Furthermore, independently of serum phosphate, high FGF23 associates with mortality and left ventricular hypertrophy in dialysis patients and with atherosclerosis in elderly individuals in the general population. FGF23 also predicts a high risk for death and cardiovascular events in predialysis CKD patients and in subjects with coronary artery disease. A recent trial in CKD patients showed that low phosphate intake associated with a phosphate binder produces a 35% decrease in plasma FGF23. Yet in this and in another trial testing several phosphate binders, FGF23 levels remained well beyond the upper limit of the normal range. Of note, in this latter study, calcification of the coronary arteries and abdominal aorta actually increased, rather than decreased, during treatment with these drugs in the face of evidence of negative phosphate balance and amelioration of hyperparathyroidism. Mechanistic studies are still needed before testing the hypothesis that FGF23 is implicated in a causal manner in cardiovascular and renal diseases. Given the modest effects of phosphate binders on serum FGF23 in CKD patients, pharmacologic interventions antagonizing the effects of this growth factor rather than phosphate-lowering interventions should be put in place to properly test this hypothesis in the clinical scenario in CKD.

Background In this study, we examined the relative usefulness of serum copeptin levels as a surrogate marker of vasopressin (AVP) in adult polycystic kidney disease (ADPKD) by correlating it with baseline and longitudinal changes in markers of both renal function and common CVD manifestations (hypertensive vascular disease, atherosclerosis and endothelial dysfunction) that accompany the progression of this disease. Methods We studied a cohort of young and otherwise healthy ADPKD patients (n = 235) and measured cardiovascular function using flow-mediation dilatation (FMD), carotid intima media thickness (cIMT) and pulse wave velocity (PWV), as well as serum copeptin (commercial ELISA, a stable marker of AVP activity). The same analyses were carried out at baseline and after 3 years of follow-up. Results At baseline, median eGFR was 69 mL/min./1.73 m2, mean FMD 6.9 ± 0.9%, cIMT 0.7 ± 0.1 mm, and PWV 8.1 ± 1.2 m/s. At follow-up, equivalent values were 65 (44–75) mL/min./1.73 m2, 5.8 ± 0.9%, 0.8 ± 0.1 mm. and 8.2 ± 1.3 m/s. with all changes statistically significant. Plasma copeptin also rose from 0.62 ± 0.12 to 0.94 ± 0.19 ng/mL and this change correlated with ΔeGFR (-0.33, p 0.76], and ΔPWV [cut-off:≤7.80]. Conclusions Vascular dysfunction as reflected by FMD and cIMT, but not PWV or an altered cardiac geometry, precede most other signs of disease in ADPKD but is predicted by elevated levels of the circulating AVP-marker copeptin.