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Background Patients with atrial fibrillation (AF) and severe chronic kidney disease (CKD) are at higher risk of both bleeding and thromboembolic events. Non-vitamin K antagonist oral anticoagulants (NOACs) are licensed to be used in these patients, although they were excluded from phase III controlled randomized trials comparing NOACs vs warfarin in AF. Thus, current evidence on NOACs use in such setting of patients is not definitive. Purpose Aim of our multicenter study was to perform a real-world comparison of clinical outcome with NOACs vs vitamin K antagonist anticoagulants (VKAs) also in AF patients having an estimated glomerular filtration rate (eGFR) 15–29 mL/min. Methods We retrospectively included a total of 266 patients receiving NOACs (N=159) or VKAs (N=107). Primary outcome measure was the cumulative incidence of the net composite endpoint including ischemic stroke, systemic thromboembolism or any bleeding. Mean follow-up was 2.6 years. Results CHA2DS2-VASc and HAS-BLED scores at baseline were similar in the two groups (3.4±1.3 with NOACs vs 3.4±0.9 with VKAs and 3.1±1.0 vs 3.0±0.7, respectively); eGFR and hemoglobin values were also comparable (31.8±12.3 vs 32±11.9 mL/min and 10.2±2.1 vs 11.0±2.3 g/dL, respectively). NOACs were not inferior to VKAs for the primary net composite endpoint: incidence 20.7% vs 29.9%, p Conclusions Our real-world data indicate that in patients with AF and severe renal failure NOACs are not inferior to VKAs for both safety and efficacy. The use of NOACs was associated with a numerically lower incidence of minor bleeding. Funding Acknowledgement Type of funding source: None

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.

According to the recent definition proposed by the Consensus conference on Acute Dialysis Quality Initiative Group, the term cardio-renal syndrome (CRS) has been used to define different clinical conditions in which heart and kidney dysfunction overlap. Type 1 CRS (acute cardio- renal syndrome) is characterized by acute worsening of cardiac function leading to AKI (5, 6) in the setting of active cardiac disease such as ADHF, while type - 2 CRS occurs in a setting of chronic heart disease. Type 3 CRS is closely link to acute kidney injury (AKI), while type 4 represent cardiovascular involvement in chronic kidney disese (CKD) patients. Type 5 CRS represent cardiac and renal involvement in several diseases such as sepsis, hepato - renal syndrome and immune - mediated diseases.

La sindrome cardio-renale (SCR) è una sindrome clinica ben nota, che descrive tanto gli effetti negativi dell'insufficienza renale sull'equilibrio cardio-circolatorio quanto quelli dell'insufficienza cardiaca sulla funzione renale. Molti autori hanno studiato l'utilità di marcatori sierologici ai fini dell'identificazione e del monitoraggio ambulatoriale delle varie forme di questa sindrome. L'analisi dei livelli sierici dei peptidi natriuretici è, al momento, quella maggiormente utilizzata, in quanto essi stessi non sono solo direttamente associati alla gravità delhinsufficienza cardiaca, ma anche capaci di rilevare precocemente la disfunzione renale, certamente prima che sia possible osservare un incremento nei livelli sierici di creatinina. NGAL, cistatina C, NAG, KIM-1 e IL-18 rappresentano interessanti biomarcatori per la diagnosi precoce di danno renale acuto (AKI), e quindi per la diagnosi precoce delle forme renocardiache acute, mentre il loro utilizzo in altre forme di SCR non appare codificato. Al contrario, la valutazione di KIM-1 e IL-18 sembra più utile per cercare una diagnostica differenziale tra forme diverse di insufficienza renale acuta. (Cardionephrology)

Atrial fibrillation (AF) represents the most common arrhythmia in patients with chronic kidney disease (CKD). As in the general population, in CKD patients AF is associated with an increased risk of thromboembolism and stroke. However, CKD patients, especially those on renal replacement therapy (RRT), also exhibit an increased risk of bleeding, especially from the gastrointestinal tract. Oral anticoagulation is the most effective form of thromboprophylaxis in patients with AF presenting increased risk of stroke. Limited evidence on efficacy, the increased risk of bleeding as well as some concern regarding the use of warfarin in CKD, has often resulted in the underuse of anticoagulation CKD patients. A large body of evidence suggests that non-vitamin K-dependent oral anticoagulant agents (NOACs) significantly reduce the risk of stroke, intracranial hemorrhage, and mortality, with lower to similar major bleeding rates compared with vitamin K antagonist such as warfarin in normal renal function subjects. Hence, they are currently recommended for patients with atrial fibrillation at risk for stroke. However, NOACs metabolism is largely dependent on the kidneys for elimination and little is known in patients with creatinine clearance

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.

Fungal peritonitis represents an infectious life-threatening complication in chronic kidney disease patients on peritoneal dialysis (PD). It causes more than 25% mortality rates (1, 2) often leading to patients' drop out from PD, Tenckhoff catheter removal and hospitalization. Causative diagnosis is often delayed because of non-specific clinical signs and symptoms in respect of bacterial infections and slow mycotic spores growth in coltures. Catheter removal is quickly recommended after microbiological or cultural mycotic identification based on International Society for Peritoneal Dialysis Guidelines/Recommendation 2010 update (3). Furthermore, international guidelines provide only few specific hints about drug choice, dosage, combination and length of antimycotic therapy; we must treat our patients for weeks or months most often.Our clinical report refers to a 70 years old woman, on APD (Automated Peritoneal Dialysis), who developed a fungal peritonitis by Aspergillus niger. Tenckhoff catheter was immed...

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...

This multicentre phase II study was aimed at investigating the activity and safety of pegylated liposomal doxorubicin (PLD) and gemcitabine (GEM) as front-line therapy in a large series of chemotherapy-naïve recurrent/metastatic breast cancer patients. From June 2003 to December 2006, a total of 71 recurrent/metastatic breast cancer patients were enrolled. Median age was 63 years (range=37-79), and 31 patients (43.7%) wereor =65 years old. Patients received PLD, 25 mg m(-2), day 1, followed by GEM, 800 mg m(-2), days 1 and 8, q21. Response was evaluable in 64 cases. Eight complete (12.5%) and 17 partial responses (26.6%) were registered, with an overall response rate of 39.1%. Thirty patients (46.9%) experienced stable disease, with an overall clinical benefit of 85.9%. Median time to progression (TTP) was 11 months, whereas median overall survival (OS) was not reached. The rate of 1- and 2-year OS was 79 and 61%, respectively. A total of 443 courses were evaluable for toxicity: grade 3 and 4 neutropaenia affected 14 patients (20.3%) and 3 patients (4.3%), respectively. Grade 3 and 4 palmar-plantar erythrodysesthesia syndrome was documented in five cases (7.2%) and one case (1.4%), whereas grade 3 and 4 mucositis occurred in six cases (8.7%) and two cases (2.9%), respectively. Grade 2 cardiac toxicity was observed in only one case. Interestingly enough, there was no difference in the percentage and severity of either haematological or non-haematological toxicity according to the age of the patients (65 vsor =65 years). We confirmed in a large, very homogenous study sample of chemotherapy-naïve recurrent/metastatic breast cancer patients the efficacy and safety of PLD/GEM combination, providing response rates, median TTP and OS values comparable with those achieved with more toxic combinations.

This multicentre phase II study was designed to evaluate the antitumour activity and toxicity of bifractionated camptothecin (CPT-11) and 5-fluorouracil/ leucovorin (5-FU/LV) in the treatment of patients with metastatic colorectal cancer (MCC) who had been pretreated with 5-FU/LV-oxaliplatin (FOLFOX regimen). In all, 35 patients were enrolled in a two-stage trial. Treatment consisted of two daily doses of CPT-11, 90 mg m2 administered over 90 min, followed by LV, 200 mg m2 administered over 2 h plus 5-FU 400 mg m2 as a bolus and 600 mg m2 as a 22-h continuous infusion administered with disposable pumps as outpatient therapy. Toxicity was closely monitored. Response was evaluated by computed tomography scans every 8 weeks. All 35 patients were assessable for toxicity and response to treatment. Seven patients had a partial response, giving an overall response rate of 20%; 11 patients had stable disease (31.4%) and 17 progressed (48.5%). The median progression-free survival was 7.1 months and median survival was 14 months. A total of 10 patients (30%) experienced grade 3-4 toxicity, including nausea (15%), diarrhoea (12%) and neutropenia (15%), while seven patients (21%) had grade 2 alopecia. The bifractionated bimonthly schedule of CPT-11 plus 5-FU/LV showed substantial antitumour activity and was well tolerated in this group of patients with a poor prognosis, pretreated with the FOLFOX regimen.

TAPSE measurement during echocardiography is a well known measure of right heart systo-diastolic function. Low TAPSE means reduced cranio-caudal excursion of tricuspidal annulus, sign of both reduced ejection fraction and reduced distensibility of right ventricle. It is a good prognostic index for cardiac mortality risk in CHF patients, adding significant prognostic information to NYHA stadiation. Nephrologists do not always fully aware of right ventricular function in their patients affected by chronic renal failure (CRF), even if this datum is probably crucial in vascular access policy. Our study was designed to study right ventricle function and TAPSE on 202 patients affected by moderate chronic renal failure, free from overt pulmonary hypertension. TAPSE, PAPs, right chambers diameters, classical Framingham factors, estimated glomerular filtration rate were recorded. TAPSE was reduced (23 mm) in 43% of patients enrolled, while dilated right chambers were present in 24%. PAPs exceeded 30 mmHg in 29% of patients. Echocardiographic signs of left ventricular hypertrophy were found in 36% of patients. The ejection fraction was normal in all patients. Statistical analysis showed a significant indirect correlation between TAPSE and PAPs and between TAPSE and tele-diastolic diameters and volumes of the right ventricle, while a direct correlation was observed between TAPSE and Framingham score. TAPSE showed a bimodal distribution, with a subpopulation "low TAPSE - high PAPs", next to a population characterized by normal values ??for both parameters. A reduction in compliance and systolic function of the right heart chambers is quite early and frequent in course of CKD, a fact that the nephrologist should take in due consideration, managing blood volume or planning vascular access for hemodialysis.La misurazione dell'indice TAPSE nel corso di un esame ecocardiografico rappresenta un parametro ben codificato per la studio della funzione sisto – diastolica del cuore destro.Bassi valori di TAPSE indicano una ridotta escursione cranio – caudale dell'anulus tricuspidale, a sua volta indice di ridotta frazione d’eiezione e distensibilità del ventricolo destro.Al tempo stesso rappresenta un buon indice prognostico per il rischio di mortalità cardiovascolare in pazienti affetti da malattia renale cronica e conferisce ulteriore valore prognostico alla sola stadiazione NYHA.I nefrologi non sono ancora del tutto consapevoli dell’importanza dello studio della funzione ventricolare destra nei pazienti affetti da malattia renale cronica (CKD) anche se il dato sembra essere cruciale soprattutto in vista di una buona politica riguardante il confezionamento dell’accesso vascolare per emodialisi.Il nostro studio è stato progettato per valutare la funzione ventricolare destra e la TAPSE in 202 pazienti affetti da Malattia Renale Cronica di grado moderato senza segni clinici evidenti di ipertensione polmonare.Sono stati presi in considerazione i seguenti parametri: TAPSE, PAPs, diametri delle sezioni cardiache di destra, fattori di rischio di Framingham e stima della frazione di filtrazione glomerulare.I valori di TAPSE erano ridotti (23 mm) nel 43% dei pazienti arruolati, mentre il 24% dei pazienti esaminati presentava dilatazione delle camere cardiache di destra con PAPs superiori ai 30 mmHg nel 29% dei pazienti. Segni ecocardiografici di ipertrofia ventricolare sinistra sono stati riscontrati nel 36% dei pazienti. La frazione di eiezione era normale in tutti i pazienti studiati.L’analisi statistica dei dati ha evidenziato una significativa correlazione indiretta tra TAPSE e PAPs e tra TAPSE e diametri/volumi del ventricolo destro, mentre una correlazione diretta è stata trovata tra TAPSE e punteggio di Framingham.I valori di TAPSE si sono distribuiti in maniera bimodale con una sottopopolazione “a bassi valori di TAPSE ed alti valori di PAPs” vicina ad un’altra caratterizzata dalla presenza di valori normali per entrambi i parametri.Una riduzione della compliance e della funzione sistolica delle sezioni cardiache destre rappresenta un elemento precoce e frequente in corso di CKD, elemento che va tenuto in considerazione dai nefrologi allo scopo di controllare in maniera ottimale lo stato d’idratazione dei pazienti e pianificare una buona politica di allestimento di un accesso vascolare per emodialisi.

Dyspnea is an extremely common symptom among patients on dialysis [1–3]. At first instance nephrologists generally considers it as a symptom of volume overload in patients with uremia and manages it by gradually reducing the patient’s dry weight. Here we describe two clinical cases in which echocardiography proved to be a very useful tool in the differential diagnosis of dyspnea in patients on hemodialysis.

In vitro and in vivo studies have shown that oxaliplatin (L-OHP), 5-fluorouracil (5-FU) and leucovorin (L) have a synergistic activity on metastatic colorectal cancer (MCC). In order to better exploit the synergism of action between the three drugs, L-OHP was administered over 2 days, together with 5-FU-L, in a cohort of patients with MCC that had been pre-treated with chemotherapy. Forty-six patients were entered into the trial. All had been pre-treated with chemotherapy for metastatic disease: 14 with the 'de Gramont' regimen alone, and 32 with the same regimen combined with irinotecan (CPT-11). The outpatient treatment consisted of L-OHP 50 mg/m(2), followed immediately by the 'de Gramont' regimen. All drugs were administered on days 1 and 2, every 14 days. Median patient age was 65 years (range: 46-78), male/female ratio was 29/17. All 46 patients were evaluated for response and toxicity. We observed 1 complete response (2.2%) and 14 partial responses (30.4%), giving an overall response rate of 32.6% (95% CI: 19.5-48.06%); 22 patients had stable disease (47.8%) and 9 patients progressed (19.6%). After a median follow-up of 13 months, median time to progression was 6.4 months (range: 3.1-31.2+), while overall median survival was 12.2 months (range: 3.7-31.2+). Toxicity was manageable: grade 3 or 4 neutropenia was observed in 33% of patients, while only 6% of patients had grade 1-2 neurotoxicity. The fractionated bimonthly schedule of L-OHP plus 5-FU-L, showed activity, with an acceptable toxicity profile, both in patients with MCC pre-treated with the 'de Gramont' regimen alone, or with this regimen associated with CPT-11.

The authors evaluated the efficacy and toxicity of the combination of carboplatin, ifosfamide, and vinorelbine in the treatment of advanced non-small-cell lung cancer. From March 1994 through March 1996, 56 previously untreated patients with stage IIIB or stage IV non-small-cell lung cancer with measurable lesions and good performance status were entered in the study. The chemotherapy schedule was as follows: carboplatin 100 mg/m2 and ifosfamide 1,500 mg/m2 with mesna on days 1, 2, and 3; vinorelbine 25 mg/m2 on days 1 and 8, every 21 days; for a total of six courses. Among 55 evaluable patients there were three complete responses (5%) and 22 partial responses (40%), for a response rate of 45% (95% confidence interval, 32-59%). The median response duration was 10.3 months (range, 2.5-27.7 months), and median survival time was 11.3 months (range, 1.1-28.1 months). The survival rate at 1 year was 48%. Toxicity included hematologic toxicity in 60% of the 247 treatment cycles administered, nausea, alopecia, and neuropathy. One pathologic complete response was observed in a patient with stage IIIB disease who became operable after four courses of chemotherapy. The outpatient treatment with carboplatin, ifosfamide, and vinorelbine shows activity in advanced non-small-cell lung cancer. The toxicity was well tolerated by patients with a good performance status.

790 Background: Aim of the study was to assess the efficacy and safety of the combination gemcitabine (GEM) and liposomal doxorubicin (PLD) in patients (pts) with measurable recurrence/metastasis f...

tion (p