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Background: Native arteriovenous fistula is the preferred vascular access in term of functionality, efficiency and complication rate. Nevertheless, research continues to seek strategies to reduce the risk of neointimal hyperplasia and hemodynamic modification. The aim of the study was to evaluate the impact on hemodynamic of the VasQ device in arteriovenous fistulae creation. Methods: The analysis included patients who underwent to fistula creation with or without implantation of the VasQ device between May and September 2019. The hemodynamic parameters were evaluated pre-operatively and at a follow-up of 1, 3, 6 months. The patency and complication rate were evaluated. Results: Fifteen VasQ devices were implanted during 30 arteriovenous fistula surgery. The baseline patients features were similar between groups (VasQ treated/control). At baseline, preoperative arterial flow was similar; radial artery diameter at surgical site was 3.4 ± 0.8 mm in treated and 2.8 ± 0.5 mm in the control group. The mean arterial flow at 1 month was 480 ± 210 mL/min in treated and 561 ± 27 mL/min in the control group. At 3 months the mean arterial flow in treated was 645 ± 143 mL/min versus 824 ± 211 mL/min ( p = 0.02) in the control group; at 6 months the arterial flow was 714 ± 146 mL/min versus 810 ± 194 mL/min ( p = 0.05) in control group. The cardiac output flow at 6 months in the treated group was 4458 ± 928 mL/min versus 5599 ± 1355 mL/min ( p = 0.05) in the control group. At 6 months the primary patency was 73% and 80% and the secondary patency 80% and 86% in treated compared to the control group, respectively. No VASQ device complications were recorded. Conclusion: The analysis of these data suggested that using VasQ device could be protective against the hemodynamic modification that occur during arteriovenous fistulae creation.

The efficacy of antiplatelet treatment with aspirin in the primary prevention of major cardiovascular events was questioned during 2018, following a new series of trials that we summarize here in a quick synoptic overview. The three studies involved are the ASPREE trial, the ASCEND study and the ARRIVE trial. These studies all have a double-blind randomized design, and 100 mg/day aspirin was administered with an intention-to-treat approach and against placebo. Age of the enrolled patients, prevalence of diabetes mellitus and geographical location of other studies are just some of the elements analyzed here, in addition to the different problems of cardiovascular events. The ASPREE study observed a marginal reduction of cardiovascular events with the use of aspirin, by approximately 5% with a confidence interval at risk of insignificancy. On the other hand, the increased risk of a hemorrhagic event appeared to be rather robust, resulting between 18% and 62%. The ASCEND study observed a reduction in cardiovascular events of around 12%, offset by an increase in the risk of major bleeding between 9% and 52%. The ARRIVE study did not detect any incidence of major cardiovascular events, while the risk of major bleeding appeared to even double. The evidences of the current literature push us to review a widespread conviction among professionals who fight the war against cardiovascular disease every day: the prescription of aspirin in the primary prevention can no longer happen systematically, and every single prescription need care between benefits and dangers connected to the treatment.

Cardiovascular disease is the main cause of morbidity and mortality in patients with chronic kidney disease (CKD) affected by a series of risk factors (hypertension, anemia, left ventricular hypertrophy, cardiac failure, and dyslipidemia). The combined presence of these factors raises the cardiovascular risk in CKD patients considerably compared with that of the general population. Nephrologists can play a role in preventing and treating these risk factors and thereby delaying the development of CKD. In preventing CKD, nephrologists who practice ultrasound techniques should have basic know-how of echocardiography so that they can screen CKD patients for early referral to a cardiologist. Echocardiography is a noninvasive ultrasound technique that requires adequately trained doctors to perform it. Nephrologists who practice it need to obtain good training and postgraduate certification of competence in echocardiography. These nephrologists should team up with cardiologists rather than replace them, and at the same time be aware that they possess the basic knowledge to manage cardiovascular disease in CKD patients.

Cardio-renal anemia syndrome. Third part: TherapyIn the previous sections of this chapter the clinical, epidemiological, pathophysiological and diagnostic aspects of cardiorenal anemia syndrome (CR...

La fistola entero-vescicale è una rara complicanza di varie malattie inflammatorie e di patologie tumorali, prevalentemente a carico del colon. La causa più frequente è rappresentata dalla diverticolite del colon-sigma. Descriviamo qui il caso di una fistola entero-vescicale comparsa in un paziente portatore di trapianto renale da donatore cadavere, esordita con i segni della pielonefrite acuta e della pneumaturia, secondaria a diverticolite del sigma pauci-sintomatica. L'ecografia del graft e della relativa via urinaria evidenziava rene di aspetto globoso con multiple aree ipoecogene parenchimali, idroureteronefrosi di II grado, presenza di fine materiale iperecogeno intrapelvico, uretere e vescica con pareti diffusamente ispessite. Veniva quindi eseguita uro-TC che confermava la pielonefrite acuta del graft ed evidenziava la presenza di livelli idroaerei in vescica e di una fistola fra sigma e parete laterale sinistra della vescica, in presenza di numerosi diverticoli del colon. La terapia antibiotica mirata con ciprofloxacina e teicoplanina, determinava significativo recupero delle condizioni generali e progressivo miglioramento del quadro clinico e laboratoristico. Successivamente, il paziente veniva sottoposto a resezione del sigma e sutura della breccia vescicale, con totale risoluzione della sintomatologia.

Le infezioni delle vie urinarie costituiscono un problema clinico frequente in tutte le età. L'ecografìa è uno strumento prezioso nella diagnosi e nel management delle infezioni, consentendo di diagnosticare rapidamente complicanze e fattori predisponenti. Questa review passa in rassegna gli aspetti ecografìci delle infezioni della vescica, della prostata, delle vesci-cole seminali, dei didimi, degli epididimi e dello scroto, fornendo un pratico strumento di consultazione rapida al nefrologo.

I pazienti affetti da malattia renale cronica possono andare incontro a tutta una serie di patologie che colpiscono il pericardio ma, sicuramente, alcune entità nosologiche sono più frequenti di altre. Gli ultimi decenni hanno assistito, per fortuna nostra e dei nostri pazienti, a un netto miglioramento per quanto concerne i protocolli terapeutici per i pazienti nefropatici e le forme tipiche di pericardite uremica, così frequenti negli anni passati, sono ormai uno sbiadito ricordo. È tuttora frequente osservare pazienti con versamento pericardico (idiopatico, ovvero secondario a malattie sistemiche), soprattutto per quanto concerne i pazienti sottoposti a trattamenti depurativi extracorporei ed i pazienti che iniziano il trattamento dialitico in condizioni di emergenza/urgenza (ad esempio, pazienti affetti da scompenso cardiaco congestizio); il versamento pericardico viene schematicamente classificato in lieve, moderato e severo in base all'interessamento più o meno globale del pericardio. Meno frequenti sono gli episodi di pericardite acuta (anch'essa idiopatica o secondaria), spesso su base virale, neoplasticae/o immunologica (vedi pazienti trapiantati in terapia immunosoppressiva). Le forme di pericardite costrittiva sono più rare a documentarsi in corso di malattia renale cronica e, in genere, rappresentano lo stadio finale di diverse patologie sistemiche: l'esito finale è, in genere, la fibrosi pericardica. (Cardionephrology)

Primary and secondary Prevention of arterial hyPertension: nePhrologist's Point of view abstract. Nephroangiosclerotic chronic kidney disease's primary and secondary prevention is actually based on blood pressure control and reduction of proteinuria. In proteinuric patients, blood pressure control has to be obtained by blocking renin-angiotensin axis, even in patients with moderate to severe chronic kidney disease. Combination therapy with angiotensin converting enzyme inhibitor (ACEi) drugs and angiotensin II receptor blockers (ARB) doesn't imply addictive protective effects. It could be tested in selected patients with proteinuria levels above 1 g/day. Combination therapy with ACEi and anti-aldosteronic agents seems to be promising but we need more multicentric trials.

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In un recente lavoro apparso su Journal of Clinical Investigation, Chen et al illustrano in maniera affascinante il ruolo cruciale dell’eritropoietina nel mantenimento della “stabilita vascolare” (1) . I nostri Autori hanno condotto uno studio dal disegno estremamente elegante sul ruolo dell’eritropoietina nella retinopatia del pre-termine. Tale patologia e caratteristica dei neonati pre-maturi, esposti ad elevate tensioni atmosferiche di ossigeno. Tale insulto induce inizialmente la vaso-obliterazione del network vascolare retinico, come risposta adattativa che tenderebbe a ridurre l’eccessivo apporto di ossigeno. A tale fase segue paradossalmente una condizione di ipossia periferica, un imponente stimolo alla neoangiogenesi, che conduce a fenomeni di massiva, disordinata angio-proliferazione patologica, assai simile a quanto si osserva nella retinopatia diabetica. L’EPO ha mostrato di svolgere un ruolo centrale nelle singole fasi della malattia. All’iniziale iperossia si associa la soppressione dei livelli tissutali di mRNA per EPO. Ne consegue quindi l’impoverimento del network micro vascolare della retina, per vaso obliterazione e ridotta neoIntroduzione

Anemia is a common complication associated with congestive heart failure (CHF) and chronic kidney disease (CKD), and is often reported as a component of the cardiorenal syndrome (CRS). The triad an...

Galectin-3 is a 32- to 35-kDa member of the galectin family of b-galactoside-binding lectins, which is characterized by a carbohydrate recognition domain. Through its carbohydrate-binding function, it regulates cell growth, differentiation, and inflammation. It also plays a complex, context-dependent role in the kidneys. During the development, it promotes nephrogenesis and is strongly expressed in the ureteric bud and its derivatives. An increase in the concentration of galectin-3 has been reported to be associated with fibrosis of the kidneys. Elevated levels of plasma galectin-3 are also associated with increased risks of rapid renal function decline, incident chronic kidney disease, and progressive renal impairment, and also with cardiovascular endpoints, infection, and all-cause mortality in patients with renal function impairment. This review discusses a general survey on galectin-3 expressions in nephrogenesis, kidney injury in animal models, clinical renal diseases, and renal transplantation and t...

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In this review we analyze the cardiorenal effects of hyperuricemia and try to answer the eternal question of whether it is or is not to be considered a true risk factor in addition to a well-established marker of cardiovascular, cerebrovascular and renal risk.

Vitamin D represents the precursor of calcitriol, crucial for bone and mineral metabolism. The high prevalence of vitamin D deficiency and the detection of vitamin D receptor (VDR) both in the heart and vessels have focused the interest on potential cardiovascular effects of vitamin D.Although several experimental data showed the protective role of vitamin D, on the other hand vitamin D “overdose” can contribute to heart and vascular calcification.Meta-analyses of randomized-controlled trials (RCTs) underlined the association of vitamin D deficiency and increased cardiovascular morbidity and mortality but no significant improvements on cardiovascular outcomes are provided by the supplementation of vitamin D.The following review provides an update on pathophysiology of vitamin D and vitamin D receptor (VDR) discussing on the association with cardiovascular risk factors and disease and on the role of vitamin D supplementation in preventing cardiovascular disease in chronic kidney disease (CKD) patients.

Cardiovascular disease (CV) is the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). The increase in cardiac complications in patients with CKD has encouraged ...

There is a great deal of data demonstrating a close association between chronic kidney disease (CKD) and cardiovascular disease, particularly coronary artery disease (CAD). About one half of deaths in patients with end-stage renal disease (ESRD) are of cardiovascular causes. The association between CKD and ischemic heart disease can be explained in part because both conditions are related to the traditional risk factors for atherosclerotic vascular disease. However, CKD might also have a casual role in the development and progression of CAD, with several mechanisms potentially involved. Among CAD patients, those with CKD have systematically a worse prognosis than those without CKD irrespective of the clinical presentation or the treatments applied. Current therapy is based on small trials and observational data and on the extrapolation of the strategies that have been proved useful in the general population, although many treatments that have been shown to improve the prognosis of CAD patients are underused in those with renal impairment. (Cardionephrology)

Is peritoneal ultrafiltration a useful therapeutic alternative in diuretic resistant heart failure, even in patients with preserved glomerular filtration rate?Some recent clinical trials, here briefly analysed, reported the positive effects of peritoneal ultrafiltration on NYHA class, hospitalization rates and quality of life of decompensated patients.Why this technique has so little fortune among Nephrologists?

Several abnormalities in chronic kidney disease-related mineral and bone disease (CKD-MBD) have emerged as novel risk factors in excess cardiovascular mortality in patients with CKD and end-stage renal disease (ESRD). Hyperphosphatemia, vascular calcifications development, and decreased active vitamin D production, leading to activation of the renin angiotensin system (RAS), have been identified as the primary cause of CKD-MBD-associated mortality in CKD. Recently, the fibroblast growth factor-23 (FGF-23), a newly discovered hormone produced in the bone that regulates phosphate and vitamin D metabolism by the kidney, has been reported as a strong predictor of adverse cardiovascular outcomes in patients with CKD and ESRD. The main physiological functions of FGF-23 are mediated by the activation of the FGF receptor/α-klotho co-receptor complexes in target tissues. Elevated FGF-23 has been associated with left ventricular hypertrophy (LVH), and it has been suggested that FGF-23 may induce myocardial hypertrophy through a direct effect on cardiac myocytes. Understanding of FGF-23's pathophysiology and mechanisms of action responsible for its negative effects will be necessary to develop therapeutic strategies to treat CKD-MBD. (Cardionephrology)

Several abnormalities in chronic kidney disease-related mineral and bone disease (CKD-MBD) have emerged as novel risk factors in excess cardiovascular mortality in patients with CKD and end-stage renal disease (ESRD). Hyperphosphatemia, vascular calcifications development, and decreased active vitamin D production, leading to activation of the renin angiotensin system (RAS), have been identified as the primary cause of CKD-MBD-associated mortality in CKD.Recently, the fibroblast growth factor-23 (FGF-23), a newly discovered hormone produced in the bone that regulates phosphate and vitamin D metabolism by the kidney, has been reported as a strong predictor of adverse cardiovascular outcomes in patients with CKD and ESRD.The main physiological functions of FGF-23 are mediated by the activation of the FGF receptor/α-klotho co-receptor complexes in target tissues. Elevated FGF-23 has been associated with left ventricular hypertrophy (LVH), and it has been suggested that FGF-23 may induce myocardial hypertroph...

Patients with chronic kidney disease (CKD) have a higher incidence of cardiovascular (acute and chronic) events, which in turn have an increased risk of progression to end-stage renal disease (ESRD) Inhibition of neprilysin, in addition to offering a new therapeutic target in patients with heart failure, could represent a potential improvement strategy in cardiovascular and renal outcome of patients with CKD. Inhibition of neprilysin by inhibiting the breakdown of natriuretic peptides, increases their bioavailability resulting in an increase in diuresis and sodium excretion and, in addition to exerting an inhibition of the renin-angiotensin-aldosterone (RAAS) system. Inhibition of RAAS, in turn, generates a series of counter-regulations that can balance the adverse effects present in CKD and heart failure (HF). The idea of blocking neprilysin is not very recent, but the first drugs used as inhibitors had an inadmissible incidence of angioedema. Among the latest generation molecules that can perform a specific inhibitory action on the neprilysin receptor and, at the same time, on the angiotensin II receptor thanks to the association with valsartan there is the LCZ696 (sacubitril / valsartan). This drug has shown promising benefits both in the treatment arterial hypertension and heart failure. It is hoped that equally positive effects may occur in CKD patients, particularly those with macroproteinuria.

La malattia autosomica dominante policistica renale (ADPKD) è la malattia genetica più comune in nefrologia. Due geni sono stati implicati nello sviluppo della malattia: PKD1 sul cromosoma 16 (85%) e PKD2 sul cromosoma 4 (15%). La ADPKD è clinicamente caratterizzata da coinvolgimento renale ed extrarenale espresso con la comparsa di manifestazioni cistiche e non cistiche. Dal momento che le complicanze cardiovascolari sono la principale causa di morbilità e mortalità, questa revisione si propone di analizzare il coinvolgimento cardiaco e vascolare in ADPKD. L'ipertensione è uno dei sintomi più frequenti e comune e si verifica in circa il 60% dei pazienti prima della comparsa di disfunzione renale. L'effetto dell'ipertensione sulla progressione verso stadi terminali della malattia renale, rende tale fattore di rischio uno dei più importanti e potenzialmente trattabili in ADPKD. L'ipertrofia ventricolare sinistra, spesso rilevata in questi pazienti, rappresenta un altro importante fattore di rischio indipendente per morbilità e mortalità cardiovascolare nella ADPKD. Altre anomalie come la disfunzione diastolica biventricolare, la disfunzione endoteliale e l'aumento dello spessore intima-media carotideo sono presenti anche in giovani pazienti con ADPKD con normale pressione sanguigna e la funzione renale ben conservata. Gli aneurismi intracranici, quelli extracranici e i difetti valvolari cardiaci sono altre manifestazioni cardiovascolari di comune riscontro nei pazienti con ADPKD. Il trattamento precoce dell'ipertensione mediante l'uso di agenti bloccanti del sistema renina-angiotensina-aldosterone potrebbe svolgere un effetto nefroprotettivo e ridurre l'insorgenza di complicanze cardiovascolari nei pazienti con ADPKD.

The autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disorder in nephrology. Two genes have been implicated in the development of the disease: PKD1 on chromosome 16 (85%) and PKD2 on chromosome 4 (15%). ADPKD is clinically characterized by renal and extrarenal involvement indicated by the onset of cystic and non-cystic manifestations. Since cardiovascular complications are a leading cause of morbidity and mortality, this review aims to analyze cardiac and vascular involvement in ADPKD.Hypertension is a common early symptom, and occurs in approximately 60% of patients before renal dysfunction. The effect of hypertension on the progression to end-stage renal disease makes it the main potentially treatable risk factor in ADPKD.Also, left ventricular hypertrophy occurs frequently in these patients representing another powerful and independent risk factor for cardiovascular morbidity and mortality in ADPKD.Other abnormalities, such as biventricular diastolic dysfunction, endothel...

Cardiovascular diseases such as coronary artery disease, congestive heart failure, arrhythmias, and sudden cardiac death represent main causes of morbidity and mortality in patients with chronic kidney disease (CKD). Their pathogenesis relates to the close linkage between heart and kidneys and involves both traditional and non-traditional risk factors. According to the well-established classification of cardio-renal syndrome, the cardiovascular involvement in chronic kidney disease is known as “type 4 cardiorenal syndrome” (chronic renocardiac syndrome).Uremic cardiopathy is mainly characterized by both left ventricular systolic and diastolic impairment, often associated to right heart dysfunction due to the presence of a vascular access for hemodialysis.The typical clinical picture is represented by left ventricular hypertrophy (LVH), the pathogenesis of which is multifactorial and closely linked to elevated blood pressure, vascular stiffness and atherosclerosis.The diagnosis is mainly made by ultrasound...

La fibrillazione atriale (FA) rappresenta la più comune forma di aritmia riscontrabile nella pratica clinica quotidiana, soprattutto nei pazienti affetti da cardiopatia ischemica cronica e da malattia renale cronica (CKD), ed è spesso correlata all’età avanzata e alla presenza di altre comorbidità, come ipertensione arteriosa, diabete mellito e vasculopatia polidistrettuale. Negli ultimi 20 anni si è assistito a un progressivo incremento dell’incidenza della fibrillazione atriale nei pazienti affetti da malattia renale cronica, soprattutto nei pazienti sottoposti al trattamento sostitutivo della funzione renale. (Cardionephrology)

Frequentemente, i pazienti in trattamento emodialitico periodico vengono sottoposti a ecografia del collo per la valutazione delle ghiandole paratiroidi. Sebbene la diagnosi di iperparatiroidismo secondario (sHPT) sia essenzialmente basata sul riscontro di elevati livelli di paratormone circolante e di alterazioni dei parametri del metabolismo minerale (calcio, fosforo), l'ecografia rappresenta, indubbiamente, un prezioso strumento per la diagnosi, il follow-up clinico e la terapia del sHPT. Viceversa, vi sono una scarsità di dati relativamente alla diagnostica ecografica della tiroide e solo pochi report riguardanti la patologia nodulare tiroidea nei pazienti emodializzati. Nel presente lavoro, riportiamo il caso clinico di un giovane di 37 anni, in cui l'ecografia del collo ha messo in evidenza la presenza di una nodularità tiroidea isolata. Descriveremo il percorso diagnostico intrapreso e le definitive conclusioni istopatologiche di questo nodulo tiroideo.

La malattia di Fabry è una disfunzione lisosomiale ereditaria, nella quale l'accumulo cronico di globotriaosilceramide (Gb3) induce danno d'organo renale, cardiaco e neurologico. Trasmessa attraverso il cromosoma X, ha un'incidenza stimata che va da un caso ogni 55000 maschi nati vivi sino a uno ogni 3100. La terapia enzimatica sostitutiva si propone come trattamento di elezione di tale patologia, capace di modificarne la storia clinica in maniera sostanziale. Questa review si propone come uno stimolo a guardare con occhi da “cardionefrologi” a questa sindrome cardio-renale sistemica. (Cardionephrology)

Type 5 cardiorenal syndrome (CRS) is a recently defined clinical syndrome for which complete epidemiological data is still missing. Type 5 CRS occurs when heart and kidneys are involved at once. The pathophysiology of type 5 CRS depends on the underlying disease. Acute type 5 CRS results from systemic processes, e.g. sepsis, infections, drugs, toxins, and connective tissue disorders such as lupus, Wegener's granulomatosis, and sarcoidosis. By contrast, the chronic type 5 CRS (i.e. cirrhotic liver disease) has a more insidious onset, as the kidney and cardiac dysfunction may develop slowly until reaching a crucial point leading to full decompensation. Diagnosis is based both on serological (biomarkers of acute cardiorenal disease, creatinine, and GFR levels) and imaging methods (echocardiography and abdominal ultrasound). Therapy is based on management of the underlying disease and treatment of cardiorenal complications (fluid therapy, drugs, and renal replacement therapy devices).

Pulmonary hypertension is defined as an increased systolic pulmonary pressure of >30 mm Hg, and it shows a 40% prevalence in hemodialysis patients due to vascular access (both central venous catheter and arteriovenous fistula). Secondary pulmonary hypertension in chronic kidney disease patients is strictly related to pulmonary circulation impairment together with chronic volume overload and increased levels of cytokines and growth factors, such as FGF, PDGF, and TGF-β, leading to fibrosis. Endothelial dysfunction, together with lower activation of NOS, increased levels of serum endothelin and fibrin storages, involves an extensive growth of endothelial cells leading to complete obliteration of pulmonary vessels. Pulmonary hypertension has no pathognomonic and distinctive symptoms and signs; standard transthoracic echocardiography allows easy assessment of compliance of the right heart chambers. The therapeutic approach is based on traditional drugs such as digitalis-derived drugs, vasodilatory agents (calcium channel blockers), and oral anticoagulants. New pharmacological agents are under investigation, such as prostaglandin analogues, endothelin receptor blockers, and phosphodiesterase-5 inhibitors.

Chronic kidney disease (CKD) patients demonstrate higher rates of cardiovascular mortality and morbidity; and increased incidence of sudden cardiac death (SCD) with declining kidney failure. Coronary artery disease (CAD) associated risk factors are the major determinants of SCD in the general population. However, current evidence suggests that in CKD patients, traditional cardiovascular risk factors may play a lesser role. Complex relationships between CKD-specific risk factors, structural heart disease, and ventricular arrhythmias (VA) contribute to the high risk of SCD. In dialysis patients, the occurrence of VA and SCD could be exacerbated by electrolyte shifts, divalent ion abnormalities, sympathetic overactivity, inflammation and iron toxicity. As outcomes in CKD patients after cardiac arrest are poor, primary and secondary prevention of SCD and cardiac arrest could reduce cardiovascular mortality in patients with CKD.

Nephroangiosclerotic chronic kidney disease's primary and secondary prevention is actually based on blood pressure control and reduction of proteinuria. In proteinuric patients, blood pressure cont...

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The treatment of membranous nephropathy is a highly controversial issue. As some patients may have spontaneous remission, in about 50% of cases the risk of treating patients with drugs that may have severe side effects is higher than the potential benefit of arresting disease progression. Some authors therefore propose exclusively symptomatic treatment; other authors use steroids and immunosuppressive drugs, alone or in association with high risk of adverse effects and often uncertain benefits. The intravenous administration of high doses of human immunoglobulins (IVIg) has been also extended to a growing number of kidney diseases including membranous nephropathy. The mechanisms through which IVIg carry out their therapeutic effect are still unclear. The present study is a retrospective and uncontrolled trial, the aim of which was firstly to verify if some patients could respond to extremely short treatment protocols, stopped when they appear to have a stable remission, thereby avoiding expensive continuation of treatment. Secondly, we aimed to verify if some patients, judged as nonresponders to a classical protocol of IVIg therapy, could respond to a more prolonged treatment.

In uremic patients, the frequency of sister chromatid exchanges appears markedly higher than in the general population. Statins are well known for their pleiotropic effects, which are independent of any reduction in cholesterol circulating levels. The aim of the present study was to determine the effects of exposure to escalating doses of simvastatin on the sister chromatid exchange rate in cultured lymphocytes in order to identify the influence of statin on genomic damage. Peripheral lymphocytic samples for culture were obtained from 25 healthy volunteers, 20 patients with documented carotid atherosclerosis and 30 atherosclerotic patients on maintenance regular acetate-free biofiltration. Hemodialyzed patients had a greater percentage of high frequency cells (50%) than healthy controls (3%) and a significantly higher average number of sister chromatid (9.82 ± 2.1 vs. 4.65 ± 2.18). The subgroup of hemodialyzed patients with high plaque score values was characterized by significantly greater values for both sister chromatid exchanges rate and high frequency cells percentage. Our findings demonstrate that there is an association between sister chromatid exchanges and high frequency cells rate and atherosclerosis in acetate-free biofiltration patients. In cultures with added simvastatin, high frequency cells percentages and mean sister chromatid exchanges levels were significantly lower than in cultures with an added vehicle alone, the reduction occurring in a dose-dependent fashion, above all in cultures from end stage renal disease patients. The findings, moreover, demonstrate new effects of simvastatin, which appeared to mitigate the expression of genomic damage in our model. However, it is not yet clear whether this effect is due to the prevention of genomic damage or to the potentiation of the DNA repair capacity. Statins may therefore have an anti-atherogenic action partly ascribable to their ability to provide protection against the development of atherosclerotic plaque.

Background/Aims: Patients with chronic renal failure show the presence of massive oxidative genome damage but the role played by dialysis is still a controversial issue. The aim of our study was to verify the genomic damage in B- and T-lymphocyte subpopulations of uremic patients after a single hemodiafiltration session. Methods: We enrolled 30 patients on maintenance acetate-free biofiltration and 25 age-matched healthy volunteers and studied chromosomal alterations. Results: Our data show that the basal levels of DNA damage, the number of sister chromatid exchanges and basal high-frequency cells levels are significantly higher in patients on hemodiafiltration than in controls and in T lymphocytes than in B cells. Conclusions: These findings suggest that hemodialytic treatment could represent a potential source of damage, maybe through the oxidative action of the extracorporeal circuit components, which might explain the well-known T-specific immunodeficiency correlated with uremia.

A newly identified cytokine, osteoprotegerin (OPG) appears to be involved in the regulation of bone remodeling. In vitro studies suggest that OPG, a soluble member of the TNF receptor family of proteins, inhibits osteoclastogenesis by interrupting the intercellular signaling between osteoblastic stromal cells and osteoclast progenitors. As patients with chronic renal failure (CRF) often have renal osteodystrophy (ROD), we investigated the role of osteoprotegerin (OPG) in ROD, and investigated whether there was any relationship between serum OPG, intact parathyroid (PTH) (iPTH), vitamin D, and trabecular bone. Serum OPG combined with iPTH might be a useful tool in the noninvasive diagnosis of ROD, at least in cases in which the range of PTH values compromises reliable diagnosis. Thirty-six patients on maintenance hemodiafiltration (HDF) and a control group of 36 age and sex matched healthy subjects with no known metabolic bone disease were studied. The following assays were made on serum: iPTH, osteocalcin (BGP), bone alkaline phosphatase, 25(OH)-cholecalciferol, calcium, phosphate, OPG, IGF-1, estradiol, and free testosterone. Serum Ca++, P, B-ALP, BGP, IGF-1, iPTH, and OPG levels were significantly higher in HDF patients than in controls, while DXA measurements and quantitative ultrasound (QUS) parameters were significantly lower. On grouping patients according to their mean OPG levels, we observed significantly lower serum IGF-1, vitamin D3 concentrations, and lumbar spine and hip bone mineral density in the high OPG groups. No correlation was found between OPG and bone turnover markers, whereas a negative correlation was found between serum OPG and IGF-1 levels (r=-0.64, p=0.032). Serum iPTH concentrations were positively correlated with bone alkaline phosphatase (B-ALP) (r=0.69, p=0.038) and BGP (r=0.92, p

The association between physical exercise (fitness) and mortality is a definite certainty in the scientific literature.Objective of this review is to analyse in depth the existing evidence of the association between fitness and tendency to develop chronic non-fatal kidney and heart events.While it is undisputed that cardio-respiratory functional capacity is to some extent correlated to physical activity throughout life, can one postulate that a similar reasoning also applies to renal function?

Calciphylaxis, better described as “Calcific uremic arteriolopathy” (CUA), involves about 1–4% of hemodialysis patients all around the world with high mortality rates. We describe a rare clinical case of CUA in peritoneal dialysis patient associated with urological disease. Penile calciphylaxis represents rare clinical complication, and an early diagnosis and multidisciplinary approach are requested. Pathogenesis is still unclear, and therapeutic approaches need more long-term clinical trials to test their efficacy and safety.

Erythropoietin (Epo) is a hydrophobic sialoglycoproteic hormone produced by the kidney and responsible for the proliferation, maturation, and differentiation of the precursors of the erythroid cell line. Human recombinant erythropoietin (rHuEpo) is used to treat different types of anemia, not only in uremic patients but also in newborns with anemia of prematurity, in patients with cancer-related anemia or myeloproliferative disease, thalassemias, bone marrow transplants, or those with chronic infectious diseases. The pleiotropic functions of Epo are well known. It has been shown that this hormone can modulate the inflammatory and immune response, has direct hemodynamic and vasoactive effects, could be considered a proangiogenic factor because of its interaction with vascular endothelial growth factor, and its ability to stimulate mitosis and motility of endothelial cells. The multifunctional role of Epo has further been confirmed by the discovery in the central nervous system of a specific Epo/Epo receptor (EpoR) system. Both Epo and EpoR are expressed by astrocytes and neurons and Epo is present in the cerebrospinal fluid (CSF). Therefore, novel functions of Epo, tissue-specific regulation, and the mechanisms of action have been investigated. In this review we have tried to summarize the current data on the role of Epo on brain function. We discuss the different sites of cerebral expression and mechanisms of regulation of Epo and its receptor and its role in the development and maturation of the brain. Second, we discuss the neurotrophic and neuroprotective function of Epo in different conditions of neuronal damage, such as hypoxia, cerebral ischemia, and subarachnoid hemorrhage, and the consequent possibility that rHuEpo therapy could soon be used in clinical practice to limit neuronal damage induced by these diseases.