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Objective: Non-adherence to antihypertensive agents leads to reduced blood pressure (BP) control. Data supporting the correlation of adherence with arterial stiffness (AS) are few. Furthermore, the causal relationship between AS and cognitive dysfunction (CO/DY) has not been clearly established. It is suggested that angiotensin II receptor blockers (ARBs) exhibit the lowest discontinuation rate among antihypertensive drugs. Design and Methods: We followed up with patients receiving monotherapy with irbesartan. CO/DY was assessed with the Mini-Mental State Examination (MΜSE) and other tests. Results: Patients [n=77; mean age: 56±11 years; 39 men (50.6%)] were followed-up for 16.1±10.9 months. At the end of follow up, significant reductions were observed in mean peripheral systolic BP (135±117 vs 153±11 mmHg; p : AS indices [carotid-femoral pulse wave velocity and augmentation index] also improved significantly: 7.7±1.4 vs 8.2±1.4 m/sec (p : At the end of the study, a significant improvement was observed in the MMSE test (29.7±0.7 vs. 29.2±0.9; p : The level of adherence was high in 60/77 (77.9%), medium in 9/77 (11.6%) and low in 8/77 (10.38%) patients. Conclusions: Hypertensive patients receiving mono-therapy with an ARB showed reduced AS, cognitive improvement, significant reductions in BP (peripheral and central) and decreased 24h urinary albumin excretion.

Objective The efficacy of renal sympathetic denervation (RDN) has been affirmed by a number of recent clinical studies, despite controversies in this field over the last five years. Therefore, it is of paramount importance that hypertension experts debate the merits of RDN by revealing and expressing their personal beliefs and perspectives regarding this procedure. Methods A cross-sectional survey was conducted among Greek leaders of the Hypertension Excellence Centers with the use of a closed-type questionnaire specifically designed to elicit information and evaluate the respondent's views and perspectives about RDN efficacy, safety and ideal target patient population. Results A total of 36 participants completed the survey. Based on the results, RDN was considered efficient (91.7%) and safe (94.5%), while the overwhelming majority of the participants felt confident in the long-term efficacy (88.9%) of the intervention and that it lacks reliable predictors of blood pressure response (94.5%). Patients with resistant (91.7%), ultra-resistant (94.4%), and uncontrolled hypertension (80.6%) were suggested as ideal candidates for RDN. Establishing a close co-operation between interventionalists and hypertension experts was considered essential to ensure the efficacy (97.2%) as well as the safety (97.3%) of the procedure. Conclusion The vast majority of Greek hypertension experts surveyed were convinced of the efficacy and safety of RDN based on the preponderance of available scientific and clinical data. Identification of the ideal patient group remains controversial. Respondents generally agreed on the necessity of building close collaborative relationships between interventionalists and hypertension experts in order to improve RDN clinical outcome.

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

This study aimed to assess the reliability of opportunistic screening programs in estimating the prevalence, treatment, and control rate of hypertension in the general population. Two recent epidemiological surveys obtained data on hypertension in the adult general population in Greece. The EMENO (2013–2016) applied a multi-stage stratified random sampling method to collect nationwide data. The MMM (2019) collected data through opportunistic (voluntary) screening in five large cities. Hypertension was defined as blood pressure (BP) ≥ 140/90 mmHg (single occasion; average of 2nd–3rd measurement; electronic devices) and/or use of antihypertensive drugs. Data from a total of 10,426 adults were analyzed (EMENO 4,699; MMM 5,727). Mean age (SD) was 49.2 (18.6)/52.7 (16.6) years (EMENO/MMM, p

End-stage renal disease is considered to influence coronary microcirculation and left ventricular (LV) diastolic function. We investigated whether differences exist in LV diastolic function indices and coronary flow reserve (CFR) between patients on hemodialysis (HD) and peritoneal dialysis (PD). A complete transthoracic echocardiographic study was performed on 21 HD and 22 PD patients and LV diastolic function was evaluated. CFR was estimated using transthoracic Doppler echocardiography on the left anterior descending artery, during high-dose dypiridamole infusion. HD and PD groups did not differ regarding Doppler-derived diastolic indices, but they significantly differed in the frequency of severe LV hypertrophy (38.1% in HD vs 4.5% in PD group, p = 0.009) and grade II diastolic dysfunction (42.9% in HD vs 4.5% in PD group, p = 0.004). No patient had restrictive filling pattern. There was no difference in the prevalence of arterial hypertension and diabetes mellitus in patients with grade II vs less than grade II dysfunction. Mean CFR was similar in the HD and PD groups (2.25 ± 0.65 vs 2.36 ± 0.76, p = 0.635) and lower in patients with grade II diastolic dysfunction (1.87 ± 0.43 vs 2.44 ± 0.72, p = 0.023) and diabetes (1.70 ± 0.59 vs 2.39 ± 0.68, p = 0.04). LV mass index was negatively associated with CFR (r = − 0.308, p = 0.045). Patients on HD had more advanced diastolic dysfunction compared to PD, independently of the presence of hypertension and diabetes. CFR did not differ between HD and PD patients, but it was significantly lower in diabetics and in patients with more advanced diastolic dysfunction.

The role of vitamin D in maintaining a healthy cardiovascular (CV) and the renal system has received increasing attention. Low vitamin D levels are associated with the incidence of hypertension, cardiac remodeling, and chronic congestive heart failure. Low vitamin D levels also influence renal disease progression and albuminuria deterioration. Moreover, recent research indicates that vitamin D deficiency can be a potential risk factor for coronavirus disease-19 (COVID-19) infection and poorer outcomes. Data are inconclusive as to whether supplementation with vitamin D agents reduces CV disease risk or COVID-19 severity. Conversely, in patients with kidney disease, vitamin D supplementation is associated with an improvement in kidney function and albuminuria. This narrative review considers recent data on the effects of vitamin D on the CV and renal system, as well as its possible role regarding COVID-19 complications.

Background: Chronic kidney disease (CKD) is an increasingly prevalent disease state met with great morbidity and mortality primarily resulting from the high incidence of adverse cardiovascular outcomes. Therapeutic strategies in this patient population aim at controlling modifiable cardiovascular risk factors, including dyslipidemia. Summary: In this review article, we first provide the latest pathophysiologic evidence regarding the altered dyslipidemia pattern in CKD, followed by its contemporary management according to the latest guidelines. Moreover, we present the current progress regarding the emerging therapeutic strategies. Key Messages: The presence of renal impairment leads to alterations in cholesterol structure, metabolism, and reverse transport paired with increased oxidative stress. Statins remain the cornerstone of dyslipidemia management in patients with kidney dysfunction who are at risk for cardiovascular events. However, their efficacy is debatable in end-stage renal disease under renal replacement therapy. Therefore, novel treatment approaches aiming at hypertriglyceridemia, proprotein convertase subtilisin/kexin type 9, and lipoprotein(a) are under rigorous investigation while the research of gut microbiome might provide additional mechanistic and therapeutic insight.

Background and Aims Advanced chronic kidney disease (CKD) is characterized by elevated expression of the proinflammatory and pro-atherogenic CD14++CD16+ monocytes subset. The role of lymphocyte subpopulations including natural killer (NK) cells and CD4+CD25+ regulatory T cells (Tregs) in the modulation of inflammation and immunity and subsequent cardiovascular implications have received increasing attention. The role of immune cell subpopulations remains to be determined in peritoneal dialysis (PD) patients. The aim of this pilot study was to investigate potential correlations between blood levels of CD14++CD16+ monocytes, NK cells and Tregs with phenotypes of established cardiovascular disease (CVD), including coronary artery disease (CAD) and heart failure (HF) in a cohort of PD patients. Method 29 stable PD patients (mean age 66.96 years ±14.5, 62% males) were enrolled. Exclusion criteria were a history of malignancy, autoimmune disease, active or chronic infections and a recent (< 3 months) cardiovascular event. Demographic, laboratory and bioimpedance measurements data (overhydration, extracellular and total body water and their ratios) were collected. The analysis of peripheral blood immune cell subsets was performed using flow cytometry (FC). Additionally, in 7 PD patients the distribution of the immune cells was evaluated by FC at two time points: T0 (before initiation of PD - CKD stage G5) and T1 (after PD start). Results The median dialysis vintage was 34.5 (range 3.2-141) months. Overall, PD patients had 527 ± 199 monocytes and 1731 ± 489 lymphocytes while mean percentage of CD14++CD16+ monocytes was 9.3 ±6.36% (normal range 2-8%), NK cells 16.6±10.3% (normal range 5-15%) and Tregs 2.1±1.76% (normal range 1-3%). There was no correlation of either of these cell subpopulations with age, PD vintage, inflammation markers (CRP, fibrinogen, albumin, hsTroponin-I), overhydration markers or comorbidities. Only increased NK cells were associated with the presence of HF in PD (24.87 vs 14.92%, p 0.047). In multiple regression analysis, NK cells levels were strongly associated with the presence of edema (beta coef=13.7, p Conclusion Our study is the first to evaluate the potential association between specific immune cell subsets and cardiovascular disease in long-term PD patients. Increased NK cells levels directly correlate both with the presence of HF and CAD in PD patients. Longitudinal results suggest that CD14++CD16+ and NK cells remain increased after PD start, while Tregs decrease further. The state of pro-inflammation and immune deregulation appear to persist after initiating PD. Future research is required to evaluate the role of immune cells subsets as potential tools to identify patients who are at the highest risk for complications and to guide interventions that may improve clinical outcomes.

Patients with solitary kidneys (SKs) are at risk of hypertension (HT) and associated end‐organ damage. The authors aimed to evaluate whether children with congenital SKs (CSKs) have higher office, ambulatory, or central blood pressure (BP), increased arterial stiffness or left ventricular mass index, or any risk for arrhythmia. With this purpose, patients with CSK and healthy controls being followed up between January 2018 and June 2019 were enrolled in the study. Demographic, biochemical, and office blood pressure (BP) data were recorded. Then, ambulatory blood pressure monitoring (ABPM) and measurements of central BP (cBP), pulse wave velocity (PWV), and augmentation index (AIx@75) were obtained. Ventricular repolarization parameters were acquired by 12‐lead electrocardiography. Left ventricular mass index (LVMI) and abdominal aortic stiffness parameters including strain, pressure strain elastic modulus (Ep), and normalized Ep (Ep*) were calculated with echocardiographic measurements. Finally, 36 children with CSK and 36 healthy controls were included. Serum creatinine, uric acid, total cholesterol levels, ABPM parameters, cBP levels, and PWV values were significantly higher, and eGFR levels were significantly lower in the CSK group. VR parameters, abdominal aortic stiffness indices, and LVMI were similar between the groups. CSK increased the risk of HT in ABPM (HTABPM) by 6 times. PWV was significantly correlated with Ep and Ep* in cases with CSK. Determination of cBP and PWV along with 24‐hour ABPM would be a useful tool in children with CSK.

Hypertension is a major risk factor for cardiovascular disease and is associated with functional and structural changes in the heart and the vessels. Left ventricular deformation imaging with 2D Strain Echocardiography (2DSTE) and stress echocardiography with a vasodilator,such as dipyridamole (DIPSE), are useful tools for the detection of early myocardial abnormalities in hypertensive patients The aim of the current study was to investigate whether early (relatively healthy) hypertensive patients with normal left ventricular (LV) ejection fraction may differ in 2D Strain indices at baseline and in response to a stress test such as dipyridamole, compared to healthy controls. In the current study, the associations of 2DSTE indices and their changes following DIPSE with other studied parameters were also assessed. Forty-seven male hypertensive patients (aged 57±9 years) with normal ejection fraction and without left ventricular hypertrophy and 20 healthy male subjects were studied with conventional and 2D Strain echocardiography at rest and post DIPSE. Coronary flow reserve (CFR) in the left anterior descending artery following DIPSE was also evaluated. Global longitudinal strain (GLS) and TWIST were higher while UNTWIST rate was lower in hypertensives versus controls (p DIPSE-induced changes did not differ between the groups after adjustment for age and BMI (p>0.05 for all). DIPSE-induced improvement in GLS was associated with higher CFR only in hypertensive patients (r −0.372, p=0.010). The current study showed that well controlled hypertensive patients have mild echocardiographic differences compared to controls. Some of these differences appear to depend on age and Body mass index. A “hyper-rotation” phenomenon (higher TWIST) early in hypertension may be a compensatory mechanism to preserve global systolic LV function. Coronary microcirculatory function was impaired in hypertensive patients, albeit within normal range, and was associated with DIPSE-induced changes in myocardial long-axis systolic function. Funding Acknowledgement Type of funding sources: None.

Salt sensitivity refers to the physiological trait present in mammals, including humans, by which the blood pressure (BP) of some members of the population exhibits changes parallel to changes in salt intake. It is commoner in elderly, females, Afro-Americans, patients with chronic kidney disease (CKD) and insulin resistance. Increased salt intake promotes an expansion of extracellular fluid volume and increases cardiac output. Salt-sensitive individuals present an abnormal kidney reaction to salt intake; the kidneys retain most of the salt due to an abnormal over-reactivity of sympathetic nervous system and a blunted suppression of renin-angiotensin axis. Moreover, instead of peripheral vascular resistance falling, salt-sensitive subjects present increased vascular resistance due mainly to impaired nitric oxide synthesis in endothelium. Recent studies have shown that part of the dietary salt loading accumulates in skin. Hypertensive and patients with CKD seem to have more sodium in skin comparing to healthy ones. However, we still have not fully explained the link between skin sodium, BP and salt sensitivity. Finally, although salt sensitivity plays a meaningful role in BP pathophysiology, it cannot be used by the physician in everyday patient's care, mainly due to lack of a simple and practical diagnostic test.

Obesity and renal disease are both associated with low serum 25(OH)D. The aims of the present study were to (a) assess vitamin D status and compare serum vitamin D levels in overweight/obese versus normal-weight individuals according to eGFR and (b) assess the role of 25(OH)D in the development of secondary hyperparathyroidism (SHPT). Serum 25(OH)D, 1,25(OH)2D, parathyroid hormone (PTH), calcium, and phosphate were measured in 104 subjects with BMI > 25 kg/m2. Participants were categorized according to eGFR (ml/min/1.73m2): G1 ≥ 60 (n = 53), G2 30–59 (n = 35), and G3 15–29 (n = 16). Fifty normal-weight individuals with comparable eGFR served as controls: G1-nw (n = 23), G2-nw (n = 18), and G3-nw (n = 9). 25(OH)D levels were lower in G1 compared to those in G1-nw (21.7 ± 6.5 vs 26.5 ± 7.0 ng/ml, p = 0.005), G2 versus G2-nw (19.0 ± 6.0 vs 25.0 ± 5.2 ng/ml, p = 0.001), and G3 vs G3-nw (15.8 ± 4.7 vs 20.3 ± 4.5 ng/ml, p = 0.030). 1,25(OH)2D and PTH levels were similar in obese/overweight versus normal-weight individuals in each of the eGFR categories. Factors independently associated with low 25(OH)D levels were BMI > 25 kg/m2, lower eGFR, and female gender. Mean 25(OH)D levels were

Background: Elevated uric acid (UA) is a recognized risk factor for chronic kidney disease (CKD). This study aimed to investigate whether this association exists in dyslipidemic patients receiving multifactorial treatment.Methods: An observational study conducted in Greece including 1,269 dyslipidemic individuals followed-up in a lipid clinic for ≥3 years. Estimated glomerular filtration rate (eGFR) was calculated by CKD-EPI equation and CKD was defined as ≤60 mL/min/1.73 m2. The correlation was assessed between UA levels and the CKD risk after adjusting for potential confounding factors, after defining the following UA quartiles: Q1: 6 mg/dL.Results: After excluding patients with baseline eGFR

The incidence of hypertension (HTN) and its cardiovascular (CV) complications are increasing throughout the world. Blood pressure (BP) control remains unsatisfactory worldwide. Medical inertia and poor adherence to treatment are among the factors that can partially explain, why BP control rate remains low. The introduction of a method for measuring the degree of adherence to a given medication is now a prerequisite. Complex treatment regimes, inadequate tolerance and frequent replacements of pharmaceutical formulations are the most common causes of poor adherence. In contrast, the use of stable combinations of antihypertensive drugs leads to improved patient adherence.:We aim to review the relationships between arterial stiffness, cognitive function and adherence to medication in patients with HTN.:Large artery stiffening can lead to HTN. In turn, arterial stiffness induced by HTN is associated with an increased CV and stroke risk. In addition, HTN can induce disorders of brain microcirculation resulting in cognitive dysfunction. Interestingly, memory cognitive dysfunction leads to a reduced adherence to drug treatment. Compliance with antihypertensive treatment improves BP control and arterial stiffness indices. Early treatment of arterial stiffness is strongly recommended for enhanced cognitive function and increased adherence.

OBJECTIVES Intradialytic hypertension is estimated at 5-15% of hemodialysis patients and is associated with poor prognosis. Studies on therapeutic interventions for this entity are extremely few. We aimed to evaluate the effects of nebivolol and irbesartan on peridialytic, intradialytic, and ambulatory BP in patients with intradialytic hypertension. METHODS This is a pilot randomized-cross-over study in 38 hemodialysis patients (age: 60.4 ± 11.1 years, men: 65.8%) with intradialytic hypertension (intradialytic SBP rise ≥10 mmHg at ≥4 over six consecutive sessions]. After baseline evaluation, patients were randomly assigned to nebivolol 5 mg and subsequently irbesartan 150 mg, or vice versa. Nineteen patients received a single drug-dose 1 h before hemodialysis and 19 received the drug for a week before evaluation. A 2-week wash-out period took place before the initiation of the second drug. Patients had three respective 24-h ambulatory BP measurements starting before a midweek session. RESULTS In total, 20 (52.6%) patients received nebivolol first and 18 (47.4%) received irbesartan. Patients receiving a single dose of either drug had lower postdialysis BP (baseline: 160.2 ± 17.8/93.2 ± 13.6 mmHg; nebivolol: 148.0 ± 20.8/84.5 ± 13.1 mmHg, P = 0.013/P = 0.027; irbesartan 142.9 ± 29.9/87.2 ± 18.1 mmHg, P = 0.003/P = 0.104 for SBP and DBP, respectively). The 24-h BP presented a trend towards reduction, but was significant only for 24-h DBP in the nebivolol arm. Patients on weekly administration of either drug had lower postdialysis BP (baseline: 162.5 ± 16.8/95.4 ± 12.7 mmHg; nebivolol: 146.7 ± 16.3/91.8 ± 12.2 mmHg, P = 0.001/P = 0.235; irbesartan: 146.0 ± 23.9/85.8 ± 12.9 mmHg, P = 0.004/ P = 0.007, respectively), lower intradialytic BP and lower 24-h BP (baseline: 148.3 ± 12.6/90.2 ± 9.0 mmHg; nebivolol: 139.2 ± 10.6/85.0 ± 7.7 mmHg, P

Chronic kidney disease (CKD) is recognized as a worldwide epidemic. Hypertension commonly coexists with CKD and its prevalence is progressively increasing as kidney function declines. For patients with established CKD and/or diabetes with albuminuria, the updated hypertension guidelines have recommended a blood pressure (BP) goal

The coexistence of crescents and membranous glomerulonephritis (MGN) is a special characteristic in lupus nephritis. In the absence of the characteristic histological features of lupus nephritis, MGN with crescents should raise the possibility of two other histopathological entities: anti-GBM disease and necrotizing and crescentic glomerulonephritis. The last one includes patients with positive ANCA serology or not. Here, we describe a case of a male patient who presented with extrarenal vasculitis symptoms, acute renal failure, hematuria and nephrotic-range proteinuria. ANCA serology was positive, and the biopsy revealed crescentic vasculitis plus membranous nephropathy. Reviewing the whole literature about similar histological cases, we included 38 cases with ANCA-positive serology and 30 ones with no ANCA in serum. It seems that in the first category vasculitis symptoms predominate, while in the second one these symptoms are absent. Their histological features have no major differences. In any case, the clinical course of these patients is serious, and in most cases, immunosuppression is essential in order to avoid end-stage renal disease.

Objective:Hypertension and obesity often coexist and activation of the renin-angiotensin- aldosterone (RAS) axis plays a major pathophysiological role. Since obese hypertensive patients are less frequently controlled within-goal compared with hypertensives without obesity, we aimed to determine whet

The beneficial effects of nebivolol on arterial stiffness and endothelial dysfunction are well documented in untreated hypertensive patients and differ from nonvasodilatory β‐blockers. This study tests the hypothesis that the addition of nebivolol in predominantly African American patients with type 2 diabetes already receiving maximally tolerated doses of renin‐angiotensin system (RAS) blockers will further improve large artery compliance. Patients with type 2 diabetes and hypertension on maximal RAS blockade (n=70) were randomized to nebivolol or metoprolol succinate daily. Doses were titrated until systolic blood pressure (SBP) was

Renovascular hypertension refers to the rise of arterial pressure due to reduced perfusion of the kidney caused by the stenotic renal artery/ies. The most common cause of stenotic renal artery is atherosclerosis. Atherosclerotic renal stenosis is usually part of a systemic syndrome that involves hypertension, intrinsic renal damage, and cardiovascular morbidity. So far, large trials have not proven the superiority of interventional therapies to medical management. As a result, renal artery stenosis should be treated mainly as a coronary artery disease equivalent focusing on rigorous management of hypertension, hyperglycemia, and hyperlipidemia. Antihypertensive treatment should include renin-angiotensin system blockade medication in most cases, while HMG-CoA reductase inhibitors (statins) can be used even in chronic kidney disease with safety. Lifestyle modifications, such as cessation of smoking, and antiplatelet therapy have reduced the risk of cardiovascular events in high-risk patients.

Introduction Angiogenesis is fundamental for tumour development and progression. Thus, anti-angiogenic agents have been developed and are mainly vascular endothelial growth factor (VEGF) pathway inhibitors. However, these agents commonly exhibit cardiac and renal toxicity, proteinuria and hypertension (HT). In fact, with the use of anti-angiogenic agents a rapid dose-dependent increase of blood pressure (BP) is observed. The possible mechanisms of VEGF inhibitors-induced HT include systemic endothelial dysfunction, renal impairment as well as vascular micro- and macroangiopathy. Furthermore, the simultaneous use of non-steroidal anti-inflammatory drugs (NSAIDs) and opioids in these patients results in uncontrolled HT. Conclusion Lifestyle changes are the cornerstone of antihypertensive treatment. No clear recommendations for a specific antihypertensive agent can be made. In most cases antihypertensive management needs to be individualized to each patient. Calcium channel blockers (CCBs) are considered as first line option, while renin-angiotensin-aldosterone system (RAAS) blockers should be the agents of choice in patients with proteinuria. Centrally acting antihypertensive agents and diuretics can also be used. Careful monitoring is critical during therapy and BP should be assessed every week and before any new cycle or infusion of anti-VEGF therapy. If BP remains uncontrolled anti-VEGF treatment discontinuation should be considered. Withdrawal of anti-VEGF therapy needs also a re-evaluation of antihypertensive therapy since BP will return to the prior baseline levels.

Treatment with oral anticoagulants has been associated with worsening kidney function in patients with chronic kidney disease (CKD) as well as among patients without underlying CKD. Thus, anticoagulant-related nephropathy (ARN) is an increasingly recognized entity nowadays, mainly associated with warfarin anticoagulation. Recent evidence indicates that patients treated with the direct anticoagulants may also be at risk of ARN. However, the true incidence of anticoagulant-related nephropathy is difficult to determine. The typical histological lesion involves renal tubular occlusion by red blood cells (RBCs), tubular red blood cell casts on light microscopy and dysmorphic RBCs in the glomerulus on electron microscopy. In the absence of active glomerulonephritis or other inflammatory changes that could account for glomerular hemorrhage, the above findings confirm the diagnosis. Dabigatran etexilate was the first direct oral anticoagulant approved for stroke prevention in patients with non-valvular atrial fibrillation. In this article, we describe a rare case of dabigatran etexilate-induced nephropathy in a patient with preexisting IgA nephropathy and review the recent literature regarding this increasingly recognized entity.

Kimmelstiel and Wilson originally described nodular glomerulosclerosis as the pathognomonic lesion of diabetic nephropathy. Nevertheless, nodular glomerulosclerosis pattern can rarely occur in non-diabetic patients. In such cases, the differential diagnosis includes membranoproliferative glomerulonephritis, light or heavy chain deposition disease, amyloidosis, fibrillary and immunotactoid glomerulonephritis and chronic hypoxic or ischemic conditions. In cases that the above entities cannot be proven, the term idiopathic nodular glomerulosclerosis is given. Here, we report a case of a male patient with renal failure stage IV and non-nephrotic range proteinuria. He had a history of heavy smoking and hypertension. The kidney biopsy revealed diabetic-like lesions. However, there was no evidence of glucose impairment despite the thorough work-up at the biopsy time and thereafter. The laboratory data and the electron microscopy of the specimen could not prove any other cause of nodular glomerulosclerosis, and the final diagnosis was idiopathic nodular glomerulosclerosis. Moreover, we focus on the pathological differential diagnosis and work-up.

The Klotho gene displays an extremely shortened life span with loss of function missense mutations leading to premature multiple organ failure, thus resembling human premature aging syndromes. The transmembrane form of Klotho protein functions as an obligatory co-receptor for FGF23. Klotho and FGF23 are crucial components for the regulation of vitamin D metabolism and subsequently blood phosphate levels. The secreted Klotho protein has multiple regulatory functions, including effects on electrolyte homeostasis, on growth factor pathways as well as on oxidative stress, which are currently the object of extensive research. Klotho protein deficiency is observed in many experimental and clinical disease models. Genetic polymorphisms such as the G-395A polymorphism in the promoter region of the Klotho gene have been associated with the development of essential hypertension. The kidneys are the primary site of Klotho production, and renal Klotho is decreased in CKD, followed by a reduction in plasma Klotho. Klotho deficiency has been both associated with progression of CKD as well as with its cardinal systemic manifestations, including cardiovascular disease. Thus, Klotho has been suggested both as a risk biomarker for early detection of CKD and additionally as a potential therapeutic tool in the future.

The goal of treating hypertension in patients with diabetes is reduction of macrovascular and microvascular complications. Most current guidelines recommend more aggressive treatment goals with blood pressure (BP) targets of < 130/80 mmHg. Retrospective data analyses suggest an association between a lower BP and slower declines in chronic kidney disease (CKD) as well as greater cardiovascular (CV) risk reduction in patients with type 2 diabetes. Such recommendations, however, are not supported by appropriately powered prospective outcome trials. Indeed, several important questions regarding aggressive lowering of BP levels are still unanswered. Major limitations of most existing clinical trials of BP lowering in diabetes is the failure to either target or achieve mean systolic BP values below 130 mmHg. Data from more recent randomized trials that evaluated different levels of BP do not support a BP below 130/80 mmHg as providing further CV risk reduction and compared to levels below 140/90 mmHg. One consistent benefit of a lower BP level, however, is on reduction of cerebrovascular events. There is reasonable evidence that a lower BP level does further slow progression of advanced proteinuric kidney disease such that a BP goal < 130/80 mmHg is defensible. This review examines the data for and against aggressive BP lowering in patients with diabetes.

Obesity epidemic is in rise in almost every industrialized country and continues to be a growing problem worldwide. In fact, obesity per se has been recognized as a chronic disease. Consequently, there has been a cascade of metabolic changes initiated by the markedly risen prevalence that contributes to the increased incidence of diabetes, hypertension, and cardiovascular disease. Moreover, obesity is also associated with an increased risk of chronic kidney disease (CKD). The majority of the studies indicate a direct relationship between body mass index (BMI) and CKD risk. Moreover, current evidence emphasized the fact that central obesity measurements, such as waist circumference, could be a better predictor of CKD progression and mortality than BMI. The detrimental effects of obesity on kidney outcome have been recognized in nondialysis-dependent (NDD)-CKD patients. However, survival in overweight or obese CKD patients undergoing maintenance hemodialysis is paradoxically opposed compared with the general population. This "reverse epidemiology," however, is valid mainly for the inflammated end-stage renal disease (ESRD) patients. In fact, renal transplant recipients with higher BMI have inferior patient and graft survival compared to patients with lower BMI. This review also provides perspectives concerning the mechanisms associated with obesity, such as the renin-angiotensin-aldosterone system (RAAS) activation, and the role of leptin, adiponectin, fetuin-A, and adipose tissue, as factors that contribute to the development of CKD. Prevention strategies for CKD patients are also discussed and should be considered by clinicians.

In the general population aortic stiffening, assessed by carotid femoral pulse wave velocity (cf-PWV), is associated with cognitive dysfunction (CO/DY). Data in chronic kidney disease (CKD) are limited. This study tests the hypothesis that large artery stiffness and microvascular damage in CKD patients are related to the damage of brain microcirculation reflected by impaired cognitive function. A cross-sectional study enrolled 151 patients (mean age 58.4 years; 64.5% males; 44 patients with CKD stage 1; 47 with stage 2; 25 with stage 3; and 35 with stage 4). Cognitive impairment, assessed by the Mini Mental State Examination (MMSE), the Clock - drawing test (Clock-test), and the Instrumental Activity of Daily Living (IADL), was considered as primary outcome. We measured systolic and pulse pressures at the brachial and aortic sites and cf-PWV. Our patients revealed a significant linear deterioration in all the domains of cognitive function according to CKD stages. High values of cf-PWV (P = 0.029) and aortic pulse pressure (aPP) (P

Hypertension is a well-established risk factor for cardiovascular disease (CVD) and chronic kidney disease (CKD). Patients with CKD have significant morbidity (ie, increased risk of CVD) and progression to end-stage renal disease. Increase in albuminuria over time to levels greater than 300 mg/d, in spite of blood pressure being at goal, is an independent predictor for nephropathy progression. Data provide support, however, for reducing proteinuria by at least 30% after treatment is initiated in patients with proteinuria. Pharmacologic blockade of the renin-angiotensin-aldosterone system (RAAS) slows progression of advanced proteinuric CKD more effectively than other antihypertensive agents. In post hoc analyses, this slowed progression has been correlated to reductions in proteinuria of 30% or more after blood pressure-lowering therapy is initiated. Increases in proteinuria, in spite of blood pressure reduction, are associated with faster declines in kidney function regardless of whether RAAS blockers are used.

The incidence of type 2 diabetes is increasing in the United States, which is expected to result in an increased prevalence of microalbuminuria and higher cardiovascular risk. Microalbuminuria is an indication that a low‐level inflammatory process is ongoing. In patients with hypertension, with or without diabetes, increasing urinary albumin excretion (UAE) is associated with elevated levels of inflammatory markers, endothelial dysfunction, and platelet activation. Microalbuminuria is associated with an increased incidence of cardiovascular disease (CVD) morbidity and mortality in patients with hypertension and in those with diabetes with or without hypertension. Antihypertensive agents that modulate the renin‐angiotensin‐aldosterone system (RAAS) can delay the onset and reduce progression of microalbuminuria and decrease CVD morbidity and mortality in patients with diabetes. Clinical trials provide a spectrum of results regarding the protective effects of RAAS‐blocking agents. Consideration of baseline blood pressure (BP), UAE and CVD risk, and the extent of BP lowering with treatment is necessary when interpreting clinical trial results in patients with microalbuminuria. It remains to be determined whether targeting the underlying inflammatory process can retard or prevent microalbuminuria progression or whether treatment of microalbuminuria can prevent end‐stage renal disease or death.

PURPOSE OF REVIEW: Proteinuria, that is, more than 200 mg/day of urinary albumin, is associated with the presence of kidney disease. Its increase over time is strongly correlated with progression of nephropathy. Retrospective analyses of nephropathy outcome trials show that proteinuria reduction of 30% or more after initiation of blood pressure (BP)-lowering therapy is associated with slower nephropathy progression than lowering BP without its reduction. RECENT FINDINGS: Retrospective analyses of five large nephropathy outcome trials demonstrate that nephropathy progression slowed by an additional 28-39% over the control or placebo group when proteinuria was reduced in concert with BP. Two separate trials demonstrate that nephropathy progression was slowed to a lesser degree when BP was reduced to a similar degree, but proteinuria reduced less than 30%. These associations do not hold for those with microalbuminuria, in which BP reduction is the key element to slowing nephropathy progression. Recent cardiovascular outcome trials fail to show a relationship between reductions in proteinuria and nephropathy outcomes. This large cardiovascular endpoint trial, however, was not only powered for nephropathy outcomes but also failed to show a benefit between proteinuria reduction and cardiovascular events, a previously established observation. SUMMARY: All patients with a history of hypertension and either kidney disease or diabetes should have an annual check for albuminuria. If albumin is present in amounts of more than 200 mg/day, strategies for BP-lowering therapy should also focus on a reduction of more than 30% of urinary protein.

There is an epidemic of chronic kidney disease in the Western world, with hypertension being the second most common cause. Blood pressure control rates, while improving, are still below 50% for the United States population. The following three challenges remain for the treatment of hypertension and associated prevention of end-stage kidney disease. First, a better understanding by the general medical community of how and in whom to use renin angiotensin aldosterone system blockers is needed. Second, the appropriate initiation of fixed-dose combination therapy to achieve blood-pressure goals needs to be clarified. Finally, the subgroup of patients with kidney disease needs more aggressive blood pressure lowering.

Drugs that inhibit the renin-angiotensin-aldosterone system (RAAS) are the cornerstone of therapy for cardiovascular and renal disease because they protect against worsening outcomes in the respective target organs. Recent results from the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) have confirmed that angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) confer similar cardioprotection and renoprotection, showing little to no benefit from the combination in cardiovascular disease. It is not yet clear whether one class is superior to another for renoprotection. Whether dual RAAS blockade is more advantageous than single blockade, and in which patients, is also yet to be clearly determined. The Long-Term Impact of RAS Inhibition on Cardiorenal Outcomes (LIRICO) study will compare the cardiorenoprotective effects of ACE inhibitors and ARBs in patients with albuminuria, and clarify the role of dual blockade. Preliminary evidence that RAAS inhibitors reduce incident diabetes is intriguing. Whether ARBs can reduce incident diabetes and related cardiovascular outcomes is awaited with the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial.

Fluid and solute fluctuations during the week are the main drawbacks of conventional hemodialysis (cHD) in patients' outcomes. The aim of our study was to evaluate the influence of every other day hemodialysis (eodHD) on clinical and laboratory parameters and to compare to that of cHD. Eighteen patients on cHD were included in the study. Nine patients (group I) were randomly switched to eodHD, while the rest (group II) remained on their regular cHD. By the end of the study (12 months) we observed a reduction in body weight followed by a parallel reduction in predialysis mean blood pressure by 7 mm Hg in group I (p

Chronic kidney disease (CKD), a major worldwide public-health problem which affects about 10% of the population, has an increased annual incidence rate of about 5-8%. This increased incidence is mainly due to type 2 diabetes and hypertension and the increasing incidence of elderly patients with CKD. Although the progression to end-stage renal failure (ESRF) is mainly based upon the underlying disease, comorbid conditions such as an initial low renal function, severe proteinuria, and high levels of blood pressure also play important roles in the development of ESRF. Since experimental and clinical evidence suggest that angiotensin II plays a central role in the progression of CKD, pharmacological inhibition of the renin-angiotensin-aldosteron system (RAAS) with angiotensin converting enzyme inhibitors or angiotensin II receptor antagonists has been suggested as first-line treatment for hypertension and prevention of ESRF in these patients. Aliskiren, a novel renin inhibitor is also a promising medical intervention. However, independently of the category of the drugs used, low target blood pressure levels seem to be equally or more important for the delay or prevention of CKD. In this review the results of studies with pharmacological inhibition of the RAAS in patients with diabetic and nondiabetic nephropathy is discussed.

An 1H NMR-based metabonomic approach was used to investigate the correlation of histopathologically assessed tubulointerstitial lesions with the urinary metabolite profile in 77 patients with glomerulonephritides submitted to renal biopsy. The presence of renal damage was predicted with a sensitivity of 96% and a specificity of 99%. Patients with mild, moderate, and severe tubulointerstitial lesions were progressively differentiated from the healthy individuals in the Orthogonal Signal Correction Partial Least-Squares-Discriminant Analysis (OSC/PLS-DA) models with a statistically significant separation between those with mild and with severe lesions. The onset of the tubulointerstitial lesions is characterized by decreased excretion of citrate, hippurate, glycine, and creatinine, whereas further deterioration is followed by glycosuria, selective aminoaciduria, total depletion of citrate and hippurate, and gradual increase in the excretion of lactate, acetate, and trimethylamine-N-oxide. NMR-based metabonomic urinalysis could contribute to the early evaluation of the severity of the renal damage and possibly to the monitoring of kidney function.

Objectives: In the general population aortic stiffening assessed by carotid femoral pulse wave velocity (cf-PWV) is associated with cognitive dysfunction (CO/DY). Data in chronic kidney disease (CKD) are limited. Our study tests the hypothesis that large artery stiffness and microvascular damage in CKD patients are related to brain microcirculation changes reflected by impaired cognitive function. Methods: Among 244 patients, finally 44 with CKD stage 1; 47 stage 2; 25 stage 3; 35 stage 4, with mean age 58.4 years (64.5% males), were enrolled in a cross-sectional study. Cognitive impairment measured by Mini Mental State Examination (MMSE), Clock – drawing test (Clock-test), and Instrumental Activity of Daily Living (IADL) was considered as primary outcome. We directly measured brachial, aortic, systolic blood pressure, pulse pressure, mean blood pressure and cf-PWV. Results: Our patients revealed a significant linear deterioration in all the domains of cognitive function according to CKD stages, assessed by MMSE, Clock-test and IADL. The risk of cognitive dysfunction increased significantly from CKD stage 3 to 4 (p

We present a case which emphasizes the importance of performing a kidney biopsy in each case of acute kidney injury (AKI) of unknown etiology. The unexpected histological diagnosis of granulomatous interstitial nephritis (GIN) is a rare cause of AKI. The main causes of GIN include drugs (NSAIDs, antibiotics), sarcoidosis, and infections (mycobacterial and fungal). In our case, a 68-year-old woman was admitted with AKI, absence of symptoms and unremarkable history, apart from coronary heart disease. Renal biopsy was performed, since history as well as clinical and laboratory data could not define a cause of AKI. A more meticulous clinical and laboratory investigation followed the histological diagnosis in order to rule out sarcoidosis, vasculitis or any other known causes of GIN. Finally the diagnosis was characterized as AKI due to idiopathic GIN. The patient responded well to corticosteroids.

Alcoholic patients commonly develop a variety of acid-base and electrolyte disturbances. The aim of this review is to describe the most commonly encountered abnormalities and their significant role in the patients’ morbidity and mortality. Physicians should be aware of these clinically important disturbances caused by alcohol abuse and their underlying pathophysiological mechanisms involved for their appropriate management. Alcoholic Keto Acidosis (AKA) is a medical emergency is more common than previously thought and is characterized by an increased anion gap metabolic acidosis. However, in AKA mixed acid-base disorders are commonly observed. Alcoholic patients also exhibit severe electrolyte derangements. Multifactorial origin hypomagnesaemia is the most common electrolyte abnormality observed. Hypocalcaemia is also a frequent electrolyte disturbance and is commonly associated with hypomagnesaemia. Hypokalemia is occasionally encountered in these patients, while multifactorial origin hypophosphatemia is the second common electrolyte abnormality found. Hyponatremia is also a common electrolyte derangement and may occur subsequent to several mechanisms mediated by alcohol toxicity. Of special interest is the so-called beer potomania syndrome in poor nourished patients who consume a large amount of water with beer leading to hyponatremia. Chronic alcoholism and its comorbidities are a predisposing factor for the development of Central Pontine Myelinolisis during rapid correction of hyponatremia. Occasionally, alcoholic patients could be presented with alcohol-related intoxication mainly due to simultaneous methanol or ethylene glycol intoxication. In these cases the determination of the serum osmolal gap is used as a screening tool to identify potential toxins.

Background Vestibular neuronitis (VN) is a relatively common condition characterized by the acute onset of vertigo, nausea and vomiting, in the absence of auditory or central nervous system involvement. The exact aetiology (inflammatory, viral or vascular?) remains obscure. Lipoprotein (a) [Lp(a)] is an atherogenic particle. Its serum levels are mainly genetically determined and vary widely between individuals. Whether Lp(a) is consistently a positive acute-phase reactant is controversial. Purpose We evaluated the alterations in lipidaemic parameters and serum biological markers (including acute-phase reactants) in adult patients presenting acutely with VN. Subjects and methods A total of 34 consecutive VN patients (24 men and 11 women) and 37 apparently healthy controls (25 men and 12 women) were studied. Laboratory evaluation was performed during the acute episode and 6 months later (stable state). Results Serum Lp(a) concentrations were significantly lower at the time of presentation (median value 6·4 vs. 16·4 mg dL−1 in the stable state, P