Search

Patients undergoing abdominal aortic aneurysm (AAA) surgery with suprarenal clamping are at high risk for acute kidney injury (AKI) and major cardiac and cerebrovascular events (MACCE). We aimed to assess whether the stroke volume variation (SVV), a measure of hemodynamic instability, is associated with AKI in hypertensive patients undergoing elective AAA surgery with suprarenal clamping. In a cohort of 51 hypertensive patients, we performed serial measurements of SVV (n = 459) and serum creatinine (sCr) (n = 255). AKI was defined according to the KDIGO clinical practice guidelines. Data were analyzed by repeated-measures ANOVA and regression analysis of time-integrated changes of both SVV and sCr. AKI developed in 45% of patients (stage 1: 31%; stage 2: 10%; stage 3: 2%). The diuresis during surgery (beta − 0.29 Z-score 95% [CI − 0.54, − 0.05]; p = 0.02), clamp time (beta 0.29 Z-score [0.05–0.52]; p = 0.02), and time-integrated changes in SVV from baseline to 12 h after surgery (beta 0.31 Z-score [0.03–0.60]; p = 0.03) were independent predictors of the time-integrated changes in sCr from baseline to 48 h after the end of surgery. In a model adjusted for age and sex, patients with AKI had an increased risk for MACCE during a mean follow-up of 3.5 ± 1.1 years (HR 5.53 [1.52–20.06]; p = 0.004). SVV increases progressively during and after AAA surgery in subjects who will develop AKI. The increase of SVV precedes and predicts the rise in sCr and is a good discriminator of the development of AKI. AKI is associated with an increased long-term risk for MACCE.

Intrarenal hemodynamic alterations are independent predictors of cardiovascular events in different populations. It has been hypothesized that there is an association between renal hemodynamics and coronary atherosclerotic burden in patients with hypertension. Therefore, the present study examined the associations between renal hemodynamics, coronary atherosclerotic burden and carotid atherosclerotic disease. A total of 130 patients with hypertension aged between 30-80 years who had been referred for an elective coronary angiography were enrolled in the present study. A duplex ultrasound of the intrarenal vasculature was performed to evaluate the resistive index (RI), pulsatility index (PI) and acceleration time (AT). The carotid intima-media thickness was additionally assessed. A coronary angiography was performed to detect the atherosclerotic burden using the Gensini Score (GS). Based on the GS values, subjects were divided into quintiles (I: ≤9; II: 9-17; III: 17-30; IV: 30-44; and V: GS >44) as well as in subjects with mild (GS ≤30) or severe coronary disease (GS >30). A weak significant difference in PI was identified among quintiles (P=0.041), whereas, RI and AT did not differ significantly. PI was associated with GS in the group with low coronary atherosclerotic burden (GS ≤30; P=0.047), whereas, no association was detected in subjects with GS >30. This association remained following adjustment for age and left ventricular ejection fraction (P=0.025). In conclusion, renal vascular alterations were associated with coronary atherosclerotic burden in patients with hypertension with mild coronary disease.

Background Inflammatory bowel disease ( IBD ) is characterized by a low prevalence of traditional risk factors, an increased aortic pulse‐wave velocity ( aPWV ), and an excess of cardiovascular events. We have previously hypothesized that the cardiovascular risk excess reported in these patients could be explained by chronic inflammation. Here, we tested the hypothesis that chronic inflammation is responsible for the increased aPWV previously reported in IBD patients and that anti‐TNFa (anti‐tumor necrosis factor‐alpha) therapy reduce aPWV in these patients. Methods and Results This was a multicenter longitudinal study. We enrolled 334 patients: 82 patients with ulcerative colitis, 85 patients with Crohn disease, and 167 healthy control subjects matched for age, sex, and mean blood pressure, from 3 centers in Europe, and followed them for 4 years (range, 2.5–5.7 years). At baseline, IBD patients had higher aPWV than controls. IBD patients in remission and those treated with anti–TNFa during follow‐up experienced an aortic destiffening, whereas aPWV increased in those with active disease and those treated with salicylates ( P =0.01). Disease duration ( P =0.02) was associated with aortic stiffening as was, in patients with ulcerative colitis, high‐sensitivity C‐reactive protein during follow‐up ( P =0.02). All these results were confirmed after adjustment for major confounders. Finally, the duration of anti–TNFa therapy was not associated with the magnitude of the reduction in aPWV at the end of follow‐up ( P =0.85). Conclusions Long‐term anti–TNFa therapy reduces aPWV , an established surrogate measure of cardiovascular risk, in patients with IBD . This suggests that effective control of inflammation may reduce cardiovascular risk in these patients.

Hypomagnesemia is a common but often overlooked problem in hospitalized patients. Unrecognized hypomagnesemia can cause serious complications. The association of hypokalemia and hypocalcemia is strongly evocative of a magnesium deficiency. Research into the causes of hypomagnesemia is imperative, as it will definitely change the approach, treatment and prognosis. We report the case of a 65-year-old man with chronic hypocalcemia and hypokalemia associated with cerebellar syndrome, a solitary seizure and cerebellar hyperintensities on magnetic resonance imaging. After the detection and treatment of hypomagnesemia with oral supplements of magnesium and the replacement of pantoprazole with ranitidine, we observed immediate relief of the symptoms. In conclusion, in clinical practice, magnesium depletion should be investigated in elderly patients with hypocalcemia treated with proton pump inhibitors for many years, in particular in the presence of neurological disorders.

Scintigraphy 99mTc-sestamibi, in association ultrasound of the neck, is currently the technique of choice for the location of parathyroid adenomas in patients with hyperparathyroidism then undergo parathyroidectomy. After surgery, from 2% to 7% of patients continues to have a persistence of the disease. In this case, the sensitivity of scintigraphy with MIBI in locating ectopic parathyroid glands is limited and varies from 30% to 80%. Thanks to the introduction of a new method radiological, PET with 11C-methionine, it is now possible to detect the possible presence of parathyroid adenomas in patients with MIBI scintigraphy been examined and is also useful for false positives. PET with 11C-methionine is a diagnostic accurate in locating the parathyroid adenomas of the neck with a sensitivity of 91%, allowing you to run parathyroidectomy focused with a reduced invasiveness of surgery, with reduction of postoperative pain and better results aesthetic. In addition, a method is clinically useful in patients with secondary hyperparathyroidism and tertiary. The limits of this promising method are the poor availability of the tracer, the fact that it is executed in only four centers in Italy and the high cost. We present the cases of two patients who are diagnosed with hyperparathyroidism. They are submitted in the first instance to MIBI parathyroid scintigraphy parathyroidectomy and after removal of pathological glands. Persisting high values of PTH, patients are executed before a new scintigraphy with MIBI which is however negative and then a PET with 11C-methionine which shows accumulation of tracer in a different place not detected by scintigraphy.

Obesity is a well‐known risk factor for the development and progression of chronic kidney disease. Recently, para‐perirenal ultrasonographic fat thickness (PUFT) has shown to correlate with both total and visceral fat better than body mass index (BMI), waist circumference (WC), and other indices of obesity. Moreover, a local paracrine and mechanical action of the PUFT on kidney has been described in recent studies. Aim of our study was to assess the relationship between glomerular filtration rate (GFR) and PUFT in comparison with other anthropometric and ultrasonographic indices of adiposity. Two hundred and ninety‐six hypertensive patients were enrolled. PUFT, cutis‐rectis thickness and rectis‐aorta thickness were obtained by ultrasonography. Anthropometric measures of adiposity were also measured. Estimated GFR was calculated using the CKD‐EPI equation. Higher PUFT values were observed in patients with impaired renal function (P

Background The recent finding that aortic pulse wave velocity ( aPWV ) is increased in patients with inflammatory bowel disease may explain why the cardiovascular risk is increased despite the low prevalence of traditional cardiovascular risk factors. We aimed to test whether inflammation is associated with aortic stiffening in this setting after adjustment for major confounders and to perform subgroup analyses. Methods and Results A systematic literature search for aPWV in inflammatory bowel disease was performed using PubMed, Scopus, Web of Science, and Google Scholar databases (last accessed May 7, 2017). Inclusion criterion was peer‐reviewed publications on clinical studies reporting original data. This study followed the Preferred Reporting Items for Systematic Review and Meta‐Analyses of individual participant data 2015 guidelines. Data were provided for 4 cohorts in 3 countries (151 participants with ulcerative colitis, 159 with Crohn's disease, and 227 control patients). Using aPWV , cohort‐specific z scores were calculated after log e ‐transform and combined in meta‐analysis to form pooled effects using a random‐effects model. Compared with controls, aPWV was increased in patients with Crohn's disease (mean difference 0.78 z score; 95% confidence interval, 0.56–1.00 z score [ P z score; 95% confidence interval, 0.52–0.97 z score [ P aPWV was associated with disease duration (years, β=0.05 z score; 95% confidence interval, 0.02–0.08 z score [ P z score; 95% confidence interval, 0.02–0.11 z score [ P =0.002]) but not with markers of acute inflammation (C‐reactive protein and erythrocyte sedimentation rate), cardiovascular risk factors, and therapy. Conclusions The increased aPWV reported in patients with inflammatory bowel disease is associated with inflammation. Clinical Trial Registration URL : http://www.crd.york.ac.uk . Unique identifier: PROSPERO 2016: CRD 42016053070.

Magnesium is the second intracellular cation and the fourth most abundant mineral in the body. Low levels of magnesium have been associated with insulin resistance and type-2 diabetes mellitus, asthma, osteoporosis and chronic kidney disease (CKD). The use of proton pump inhibitors (PPIs) represents the most common cause of hypomagnesemia. The risk of hypomagnesemia, and consequently worsening of the renal function, is increased when diuretics are added to therapy in subjects treated with PPIs. Interestingly, diuretics and PPIs are two of the most used drugs in subjects with CKD. In this review, we described the mechanisms at the basis of the hypomagnesemia and the effect of this electrolyte disturbance in subjects with CKD.

Arterial stiffening is associated with increased cardiovascular risk. Whether exposure to relatively high levels of air pollution is associated with arterial stiffening is unclear. We aimed to assess the association between exposure to major air pollutants and arterial stiffening. PubMed, SCOPUS and Web of Science databases (through 31 January 2017) were searched using a combination of terms related to exposure to gaseous [nitrogen dioxide (NO2), nitrogen oxides (NOx) and sulphur dioxide (SO2)] or particulate matter pollutants (PM2.5, PM10 and PM10-2.5), arterial stiffness (pulse wave velocity) and reflected waves (augmentation index, augmentation pressure). Pertinent information were extracted from selected studies. In this systematic review were included 8 studies with available data on air pollution and arterial stiffness/reflected waves parameters (8 studies explored the effects of exposure to particulate matter pollutants, 3 studies the effects of exposure to gaseous pollutants); seven of them reported increased arterial stiffness/reflected waves after exposure to air pollution (6 of 8 studies after particulate matter pollutants; 2 of 3 studies after gaseous pollutants). Arterial stiffness and reflected waves were increased in the majority of the studies after both short- and long-term exposure to air pollutants. In conclusion, available evidence supports an association of main air pollutants with increased arterial stiffness and reflected waves. This finding may have implications for population-based strategies for the reduction of arterial stiffness, a vascular biomarker and an intermediate endpoint for cardiovascular disease.

In a recent issue of Nephron, Abu-Amer et al.[1] reported the presence of hypermagnesuria in patients following acute intravenous administration of digoxin and suggested that the Na+/K+-ATPase γ-subunit, which is the pharmacological target of digoxin, can play a role in this process. Hypermagnesuria induced by digoxin may have important clinical consequences, particularly in the presence of inherited and acquired conditions associated with hypermagnesuria and hypomagnesemia. Moreover, the co-administration of digoxin with other drugs that reduce gastrointestinal absorption (i.e., proton pump inhibitors) or increase urinary excretion (i.e., loop diuretics) may increase the likelihood of developing hypomagnesemia. In this article, we reviewed the main causes of hypermagnesuria and discussed potential drug interactions that can enhance the magnesuric effect of digoxin. We suggest that during the administration of digoxin, clinicians should consider the presence of other causes of hypomagnesemia and hypermagnesuria that could enhance the magnesuric effect of digoxin, monitor the urinary and serum levels of magnesium and prescribe an oral supplementation of magnesium.

The aim of the study was to perform an analysis of the emotional reactions, perception of stressful life and behavioural changes related to Haemodialysis (HD) in order to identify those variables that can improve lifestyle and the adherence to treatment. Some psycho- metric assessment, such as the Cognitive Behavioural Assessment, Hospital Form, (CBA- H) and the Health Survey (SF-36), which provides two indexes: the Physical Component Score (PCS) and the Mental Component Score (MCS), are suitable to assess a patient’s psychological and behavioural style and their health-related quality of life. The study involved 37 Italian out-patients with end-stage renal disease under HD therapy. We calcu- lated the Spearman correlation between variables of CBA-H, SF-36, age and time on HD. We also performed a multivariate linear regression using the CBA-H variables as predictors and PCS and MCS as dependent variables. From the CBA-H, 95% of participants self- reported psychological characteristics comparable to Type A personality, which identifies an anxious, hyperactive and hostile subject. Physical limitations were found to be directly pro- portional to the time on dialysis (rs = -0.42). The condition of perceived stress worsens the state of mental health (rs = -0.68) and general health perception (rs = -0.44). The condition of vital exhaustion correlates both the PCS and the MCS (p

Previous studies have suggested the benefits of physical exercise for patients on dialysis. We conducted the Exercise Introduction to Enhance Performance in Dialysis trial, a 6-month randomized, multicenter trial to test whether a simple, personalized walking exercise program at home, managed by dialysis staff, improves functional status in adult patients on dialysis. The main study outcomes included change in physical performance at 6 months, assessed by the 6-minute walking test and the five times sit-to-stand test, and in quality of life, assessed by the Kidney Disease Quality of Life Short Form (KDQOL-SF) questionnaire. We randomized 296 patients to normal physical activity (control; n=145) or walking exercise (n=151); 227 patients (exercise n=104; control n=123) repeated the 6-month evaluations. The distance covered during the 6-minute walking test improved in the exercise group (mean distance +/- SD: baseline, 328 +/- 96 m; 6 months, 367 +/- 113 m) but not in the control group (baseline, 321 +/- 107 m; 6 months, 324 +/- 116 m; P

Arteriovenous fistula (AVF) created with native vessels is the vascular access of choice for hemodialysis: the AVF is associated with a lower incidence of complications and longer survival than prosthetic grafts or central venous catheters [1, 2]. Nephrologists and vascular surgeons find it increasingly difficult to locate native vessels suitable for creation of a well-functioning, persistently patent AVF because of increasing prevalence among requiring dialysis patients of advanced age and comorbidities, such as diabetes mellitus and vascular disease [3].

Kidney transplantation is the treatment of choice in end-stage renal disease, given the better quality of life of transplanted patients when compared with patients on maintenance dialysis. In spite of surgical improvements and new immunosuppressive regimens, parts of transplanted grafts still develop chronic dysfunction. Ultrasonography, both in B-mode and with Doppler ultrasound, is an important diagnostic tool in case of clinical conditions which might impair kidney function. Even though ultrasonography is considered fundamental in the diagnosis of vascular and surgical complications of the transplanted kidney, its role is not fully understood in case of parenchymal complications of the graft. The specificity of Doppler is low both in case of acute complications, such as acute tubular necrosis, drugs toxicity and acute rejection, and in case of chronic conditions, such as chronic allograft nephropathy. Single determinations of resistance indices present low diagnostic accuracy, which is higher in case of successive measurements performed during the follow-up of the graft. Modern techniques such as tissue pulsatility index, maximal fractional area and contrast-enhanced ultrasound increase ultrasonography diagnostic power in case of parenchymal complications of the transplanted kidney.Il trapianto di rene è il trattamento di scelta nella malattia renale allo stadio terminale, data la migliore qualità di vita dei pazienti trapiantati rispetto a quelli che continuano il trattamento dialitico. Nonostante i miglioramenti chirurgici e nuovi regimi immunosoppressivi, parte dei pazienti trapiantati sviluppano ancora disfunzioni croniche. L’ecografia, sia in B-mode che Doppler, è un importante strumento diagnostico in caso di condizioni cliniche che possono alterare la funzione renale. Anche se l’ecografia è considerata fondamentale nella diagnosi di complicanze chirurgiche e vascolari del rene trapiantato, il suo ruolo non è pienamente conosciuto in caso di complicanze parenchimali. La specificità del Doppler è bassa, sia in caso complicanze acute, quali la necrosi tubulare acuta, la tossicità acuta da farmaci, il rigetto, sia in caso di complicanze croniche, come la nefropatia cronica del trapianto. Singole determinazioni di indici di resistenza presentano bassa accuratezza diagnostica, che è più elevata in caso di misure effettuate successivamente durante il follow-up del trapianto. Tecniche moderne, come l’indice di pulsatilità tissutale, massima frazione di zona ed ecografia con mdc aumentano le potenzialità diagnostiche dell’ecografia in caso di complicanze parenchimali del rene trapiantato.

Native arteriovenous fistula (AVF) is the vascular access of choice for hemodialysis patients. Compared with grafts and central venous catheters, AVFs last longer and are associated with fewer complications. The widespread use of the Doppler ultrasound (DUS) has increased the number of patients who are eligible for AVF by facilitating the identification of vessels that are suitable for fistula construction (preoperative vascular mapping). DUS can also extend native AVF survival by improving the early detection of complications (post-operative surveillance). It is the only imaging modality that furnishes both morphological and functional data on the native vascular access, and it is also the only imaging tool that can be used directly by the surgeon, an indisputable advantage. This review examines the numerous roles played by DUS in the construction and postoperative follow-up of AVFs, including preoperative vascular mapping, AVF maturation, and surveillance.La FAV confezionata con vasi nativi rappresenta l’accesso vascolare di scelta per il paziente emodializzato in quanto, a parità di flusso, presenta minore incidenza di complicanze e più lunga sopravvivenza rispetto alle protesi ed ai cateteri venosi centrali. L’avvento del DUS nell’armamentario di chi si occupa di chirurgia degli accessi vascolari ha, da un lato, aumentato il numero di pazienti in cui si riesce a confezionare una FAV con vasi nativi (grazie all’individuazione di vasi idonei all’intervento mediante il mapping pre-chirurgico), e, dall’altro, ha migliorato la sopravvivenza delle FAV grazie alla diagnosi precoce (monitoraggio post-operatorio) delle complicanze dell’accesso vascolare. L’eco-color-Doppler è l’unica tecnica in grado di dare informazioni sia morfologiche che di funzionalità (flusso) dell’accesso vascolare; inoltre, è l’unica tecnica (tra quelle di diagnostica per immagini) direttamente gestibile dal chirurgo e ciò rappresenta sicuramente un valore aggiunto. Questa review fornisce una panoramica sulle possibili applicazioni del DUS nell’ambito del confezionamento e del follow-up delle FAV, con particolare riferimento al mapping pre-chirurgico, alla maturazione della FAV e al monitoraggio/sorveglianza della FAV.

Background/Aims: Scarce physical activity predicts shorter survival in dialysis patients. However, the relationship between physical (motor) fitness and clinical outcomes has never been tested in these patients. Methods: We tested the predictive power of an established metric of motor fitness, the Six-Minute Walking Test (6MWT), for death, cardiovascular events and hospitalization in 296 dialysis patients who took part in the trial EXCITE (ClinicalTrials.gov Identifier: NCT01255969). Results: During follow up 69 patients died, 90 had fatal and non-fatal cardiovascular events, 159 were hospitalized and 182 patients had the composite outcome. In multivariate Cox models - including the study allocation arm and classical and non-classical risk factors - an increase of 20 walked metres during the 6MWT was associated to a 6% reduction of the risk for the composite end-point (P=0.001) and a similar relationship existed between the 6MWT, mortality (PConclusions: Poor physical performance predicts a high risk of mortality, cardiovascular events and hospitalizations in dialysis patients. Future studies, including phase-2 EXCITE, will assess whether improving motor fitness may translate into better clinical outcomes in this high risk population.

Metabolic syndrome (MetS) is currently considered to raise the risk for type 2 diabetes and cardiovascular events. It has been suggested that part of this risk excess may be due to a cluster of additional factors associated with MetS. We aimed to investigate the role of inflammation on the ventricular-vascular coupling in patients with MetS.We enrolled a total of 227 hypertensive patients (106 with MetS and 121 without MetS) matched for age and gender. Aortic pulse wave velocity (aPWV), intima-media thickness (IMT) and high sensitivity C-reactive protein (CRP) increased according to the number of MetS components. Patients with MetS showed increased aPWV (11.5 ± 3.7 vs. 10.3 ± 2.5 m/s, P = 0.03) compared with controls. In a model adjusted for age, sex, heart rate and mean blood pressure, aPWV resulted increased in patients with CKD (beta 1.29 m/s, 95%CI 0.61-1.96 m/s, P 0.001) and MetS (beta 0.89 m/s, 95%CI 0.28-1.51 m/s, P = 0.005). After additional adjustment for CRP and IMT, the slope of aPWV was respectively reduced by 16% and 62%, suggesting that inflammation and intima-media thickening could contribute to aortic stiffening in patients with MetS. In these patients, aPWV was also associated with left-ventricular mass index (beta 0.79 g/mMetS is characterized by an inflammation-dependent acceleration in cardiovascular ageing. This pattern of pathophysiological abnormalities may contribute to amplify the burden of cardiovascular risk in patients with MetS.

miRNAs are short non-coding RNAs that play a key role in the homeostasis and in the onset of many diseases. Different studies on nephropathies have identified miRNAs that are differentially expressed in nephropathic subjects compared to healthy controls. An important goal of these studies is to give the nephrologist the possibility to diagnose different nephropathies based on liquid biopsies that are less invasive for the patient than solid ones. The present review focalizes on the function of miRNAs in human physiology and renal diseases and analyzes the potential role that, in the near future, they may have in the diagnosis and treatment of acute and chronic kidney diseases.

Since many years, researchers have focused their studies to find out early sepsis biomarkers for the purpose of gaining time in the application of early goal-directed therapy protocol. Procalcitonin (PCT) is a reliable biomarker for sepsis, although it has a low specificity and prognostic value. Other recently proposed sepsis biomarkers such as interleukins, C-reactive protein (CRP), myeloid cells expressing triggering receptor-1 (TREM-1) and soluble urokinase-type plasminogen activator receptor (suPAR) still have a controversial and uncertain clinical value. In 2004 a new biomarker, soluble CD14 SubType (sCD14-ST, Presepsin), with a good performance in the diagnosis and prognostic evaluation of sepsis has been proposed. First studies highlighted that Presepsin is highly sensitive and specific at the same time. However, further studies on the clinical value of Presepsin are needed, particularly in order to explain the relationship between Presepsin and kidney failure. Indeed, Presepsin is a 13 KDa molecule theoretically totally filtered by glomerulus and reabsorbed and metabolized by proximal convoluted tubules. Therefore, the Presepsin plasmatic level could be highly influenced by an acute kidney injury in the course of sepsis or by a pre-existing chronic kidney disease. In this article we reviewed the latest evidences about the diagnostic and prognostic performances of Presepsin as a sepsis biomarker. We evaluated the usefulness of Presepsin in the context of acute and chronic kidney dysfunction. The great number of articles have been collected and the thorough revision of data from the nephrologists perspective let us consider this work exhaustive and scientifically reliable, although concise: a good starting point for the physician who wants to make use of Presepsin.

Primary and secondary glomerulonephritis are a heterogeneous group of disorders characterized by "glomerular inflammation" with an immune-mediated pathogenesis. Considering the severe side effects of the immunosuppressive drugs, the therapeutic approach remains a challenge for the nephrologists. Corticosteroids, cytotoxic agents such as cyclophosphamide, or calcineurin inhibitors such as cyclosporine and tacrolimus, azathioprine and mycophenolate mofetil can all be used for the treatment of glomerulonephritis. Several studies has been published to better understand the pathogenesis of these diseases and to identify the drugs with lower toxicity. Different mechanisms involve, directly or indirectly, the B cells in the pathogenesis of glomerulonephritis. For this reason, the attention of the nephrologists has been focused on the identification of drugs that act at this level, such as chimeric monoclonal antibodies. Rituximab, binding to the CD20 receptor expressed on the surface of B cells, induces their apoptosis and persistent depletion for 6-9 months. B cells contribute to the immune response by the maturation into plasma cells with consequent antibody production, the processing and presentation of the antigen to T cells and the production of various cytokines. For these reasons, the potential role of these drugs in the treatment of primitives and secondary glomerulonephritis is clear. In this review, we aimed to evaluate the use of rituximab in the treatment of these diseases, by focusing on the results of the most recent clinical trials.

Fungal infections have a high incidence in patients receiving peritoneal dialysis. (1) Peritoneal dialysis is often complicated by peritonitis which has only minimally mycotic etiology, but nonetheless it is associated with 15-45% mortality (8). The opportunistic pathogens such as Candida can cause infection in immunocompromised conditions. Even the Acinetobacter tends to infect immunocompromised individuals and it has the same risk factors for infection as Candida: immunosuppression, malignancy, HIV positivity and all the other conditions of immunosuppression, central venous catheterization, mechanical ventilation and prolonged antibiotic therapy. The sepsis by Acinetobacter predicts a negative prognosis with the mortality rate between 20 to 60% (12), especially in cases of isolation of multi-resistant germs. We present a case report of a CKD patient undergoing peritoneal dialysis therapy who was hospitalized for acute pancreatitis, later complicated by the development of pancreatic pseudocysts, C. albicans peritonitis with hematologic spread of the fungus, superimposed Acinetobacter baumannii sepsis and pneumonia. She has been subjected to percutaneous drainage of pseudocysts, to switch from peritoneal dialysis to hemodialysis, to various evacuative thoracentesis, and to polymicrobial therapy (meropenem, teicoplanina, tigeciclina, linezolid, colimicina, fluconazolo, etc.) that allowed the resolution of sepsis. The peculiarity of this case is represented by the numerous morbidity that the patient developed simultaneously, with the genesis of a complex clinical picture, by the combination of infections due to Candida albicans and Acinetobacter baumannii. Successful treatment strategies allowed to fight and cure a medical condition associated with a high mortality rate.

IgG4 related disease is a systemic fibro-inflammatory disorder characterized by multiple organ and multiple tissue lesions. The real pathogenesis is currentlyactually unknown. For these reasons many authors compare IgG4 related disease to sarcoidosis. Lesions are often localized in the pancreas, salivary and lacrimal glands, biliary ducts, retroperitoneum and in many other organs. The diagnosisis difficult because of mild symptoms and the possibility of mimicking other severe diseases. Therefore, histopathology together with clinical and radiological typical findings are mandatory tools for diagnosis. Steroidtherapy usually enables disappearance of tumor like lesions and complete recovery. Kidney has an extensive organ involvement in the contextof IgG4-related disease. Historically, tubule - interstitial nephritis(TIN) is considered the main renal feature of renal lesions, however recent studies extend the spectrum of renal lesions also to glomerular tuft. These findings allow to introduce in the nosography the term of IgG4related kidney disease (IgG4 RKD). This review focuses on renal involvement in IgG4related disease, in order to help nephrologists to improve their clinical, diagnostic and therapeutic approach to this emerging pleiotropic clinical pattern.

Fabry disease is a metabolic and lysosomal storage disorder caused by the functional defect of the α-galactosidase A enzyme; this defect is due to mutations in the GLA gene, that is composed of seven exons and is located on the long arm of the X-chromosome (Xq21–22). The enzymatic deficit is responsible for the accumulation of glycosphingolipids in lysosomes of different cellular types, mainly in those ones of vascular endothelium. It consequently causes a cellular and microvascular dysfunction. In this paper, we described five novel mutations in the GLA gene, related to absent enzymatic activity and typical manifestations of Fabry disease. We identified three mutations (c.846_847delTC, p.E341X and p.C382X) that lead to the introduction of a stop codon in positions 297, 341 and 382. Moreover we found a missense mutation (p.R227P) in the exon 5 of the GLA gene and a single point mutation (c.639 + 5 G > T) occurring five base pairs beyond the end of the exon 4. These mutations have never been found in our group of healthy control subjects > 2300. The studied patients presented some clinical manifestations, such as cornea verticillata, hypo-anhidrosis, left ventricular hypertrophy, cerebrovascular disorders and renal failure, that, considering the null enzymatic activity, suggest that the new mutations reported here are related to the classic form of Fabry disease. The identification of novel mutations in patients with symptomatology referable to FD increases the molecular knowledge of the GLA gene and it gives clinicians an important support for the proper diagnosis of the disease.

Vascular endothelial growth factor induces nitric oxide-dependent angiogenic effects and participates in the inflammatory response. This cytokine is over-expressed in the myocardium in experimental models of pressure overload and renal mass ablation, and vascular endothelial growth factor is increased in end-stage renal disease. We investigated the relationship between vascular endothelial growth factor, left ventricular function (by midwall fractional shortening) and mortality in a prospective cohort study in 228 hemodialysis patients.Serum vascular endothelial growth factor concentration was associated directly with interleukin-6 and tumor necrosis factor-alpha (P0.01) and inversely with albumin (P = 0.007) but was independent of the endogenous inhibitor of nitric oxide synthesis, asymmetric dimethylarginine. Vascular endothelial growth factor was inversely related with midwall fractional shortening (P = 0.002) and predicted mortality (P = 0.02). In multivariate analyses testing the involvement of this angiogenic cytokine in left ventricular dysfunction and death, these links remained substantially unmodified after adjustment for Framingham risk factors, risk factors peculiar to end-stage renal disease (Hb, Ca, P) and previous cardiovascular complications. However, these links became weaker and not significant when biomarkers of inflammation and asymmetric dimethylarginine were sequentially introduced into the multivariate models. In crude and adjusted analyses, left ventricular function was lowest in patients who displayed both high vascular endothelial growth factor and high asymmetric dimethylarginine, intermediate in patients with either high vascular endothelial growth factor or high asymmetric dimethylarginine and highest in those with low asymmetric dimethylarginine and low vascular endothelial growth factor (P = 0.001).Vascular endothelial growth factor is associated with left ventricular systolic dysfunction and mortality in hemodialysis patients. Vascular endothelial growth factor appears to be in the pathway whereby inflammation and nitric oxide inhibition lead to cardiomyopathy and death in hemodialysis patients.

Malatino LS, Stancanelli B, Cataliotti A,Bellanuova I, Fatuzzo P, Rapisarda F, Leonardis D,Tripepi G, Mallamaci F, Zoccali C (University ofCatania, Ragusa; and Clinical Epidemiology andPhysiopathology of Renal Disease and Hypertensionand Nephrology Unit, Reggio Calabria, Italy). Circu-lating E-selectin as a risk marker in patients withend-stage renal disease. J Intern Med 2007;262: 479–487.Background. E-selectin is a key adhesion moleculewhich plays a fundamental role in endothelial progen-itor cell-dependent reparative mechanisms in experi-mental ischaemia and it serves to anchor leucocytesto the endothelium in inflammatory processes. Inflam-mation is one of the strongest risk factors for deathand cardiovascular (CV) events in end-stage renal dis-ease (ESRD).Objective. The objective of the current study was toevaluate whether E-selectin is a useful biomarker ofclinical outcome in ESRD patients. We tested the pre-diction power of circulating E-selectin for mortalityand CV events in a cohort of 265 ESRD patients.Results. During the follow-up, 59 patients died and 58had CV events. All-cause mortality was inverselyrelated to serum E-selectin, the risk of death beingthe lowest in patients in the third E-selectin tertile(HR: 1, reference group), intermediate in those in thesecond tertile (HR: 1.30) and the highest in patients inthe first tertile (HR: 2.02, P = 0.01). Similarly, the riskof fatal and nonfatal CVevents followed an inverse pat-tern being lowest in the third tertile (reference group)and highest in the first tertile (HR: 1.73, P = 0.03). Theprediction power of E-selectin for death and CVeventswas confirmed in a Cox regression analysis whereE-selectin emerged as an inverse predictor of theseoutcomes, particularly so in patients with severeinflammation.Conclusions. These data are in keeping with the hypo-thesis that in systemic inflammation altered E-selectinshedding may play a role in arterial damage andimplicates this adhesion molecule in atheroscleroticcomplications in a high-risk condition like ESRD.Keywords: cardiovascularrisk,dialysis,E-selectin, ESRD,inflammation, mortality.

Clinical genetics plays a central role in the diagnostic practice, mainly due to both the hereditary and non-hereditary genetic component, which characterizes most of the diseases. This branch of medicine has been characterized by a rapid technological growth since 2003, when the entire human genome was sequenced. We need to consider the reduction in terms of both time and costs that the gene sequencing has gone through. Before, 13 years and about three billion dollars were needed, now it takes only a few weeks and about ten thousand dollars to sequence the entire human genome. The applicability of clinical genetics in nephrology is due to the fact that many kidney diseases are characterized by genetic mutations (e.g., von-Hippel Lindau syndrome, MYH9 related disorders, Fabry's syndrome, Liddle's and Bartter's Syndrome, and others). Clinical genetics plays, therefore, a crucial role since many of these diseases are often not properly diagnosed. In this review, we examine the new technologies that are available to the nephrologist for the molecular diagnosis of renal diseases.

Among the new drugs used for the treatment of Diabetes Mellitus type 2, sodium-glucose cotransporter 2 (SGLT2) inhibitors represent a promising therapeutic option. Since their ability to lower glucose is proportional to GFR, their effect is reduced in patients with chronic kidney disease (CKD). The antidiabetic mechanism of these drugs is insulin-independent and, therefore, complimentary to that of others antihyperglicaemic agents. Moreover, SGLT2 inhibitors are able to reduce glomerular hyperfiltration, systemic and intraglomerular pressure and uric acid levels, with consequent beneficial effects on the progression of kidney disease in non diabetic patients as well. Only few studies have been performed to evaluate the effects of SGLT2 inhibitors in patients with CKD. Therefore, safety and efficacy of SGLT2 inhibitors should be better clarified in the setting of CKD. In this paper, we will review the use of SGLT2 inhibitors in diabetic patients, including those with CKD.

Fabry disease (FD) is an inherited metabolic disorder caused by partial or full inactivation of the lysosomal hydrolaseα-galactosidase A (α-GAL). The impairment ofα-GAL results in the accumulation of undegraded glycosphingolipids in lysosomes and subsequent cell and microvascular dysfunctions. This study reports the clinical, biochemical, and molecular characterization of 15 members of the same family. Eight members showed the exonic mutation M51I in the GLA gene, a disease-causing mutation associated with the atypical phenotype. The clinical history of this family highlights a wide phenotypic variability, in terms of involved organs and severity. The phenotypic variability of two male patients is not related to differences inα-GAL enzymatic activity: though both have no enzymatic activity, the youngest shows severe symptoms, while the eldest is asymptomatic. It is noticeable that for two female patients with the M51I mutation the initial clinical diagnosis was different from FD. One of them was diagnosed with Familial Mediterranean Fever, the other with Multiple Sclerosis. Overall, this study confirms that the extreme variability of the clinical manifestations of FD is not entirely attributable to different mutations in the GLA gene and emphasizes the need to consider other factors or mechanisms involved in the pathogenesis of Fabry Disease.

SGLT2 inhibitors are new antihyperglycaemic agents whose ability to lower glucose is directly proportional to GFR. Therefore, in chronic kidney disease (CKD) the blood glucose lowering effect is reduced. Unlike many current therapies, the mechanism of action of SGLT2 inhibitors is independent of insulin action or beta-cell function. In addition, the mechanism of action of SGLT2 inhibitors is complementary and not alternative to other antidiabetic agents. SGLT2 inhibitors could be potentially effective in attenuating renal hyperfiltration and, consequently, the progression of CKD. Moreover, the reductions in intraglomerular pressure, systemic blood pressure, and uric acid levels induced by SGLT inhibition may potentially be of benefit in CKD subjects without diabetes. However, at present, only few clinical studies were designed to evaluate the effects of SGLT2 inhibitors in CKD. Consequently, safety and potential efficacy beyond blood glucose lowering should be better clarified in CKD. In this paper we provide an updated review of the use of SGLT2 inhibitors in clinical practice, with particular attention on subjects with CKD.

Zoccali C, Mallamaci F, Tripepi G, Cutrupi S, Parlongo S, Malatino LS, Bonanno G, Rapisarda F, Fatuzzo P, Seminara G, Stancanelli B, Nicocia G, Buemi M (Institute of Biomedicine, Clinical Epidemiology and Pathophysiology of Renal Diseases and Hypertension, Reggio Cal; University of Catania; and University of Messina, Italy). Fibrinogen, mortality and incident cardiovascular complications in end-stage renal failure. J Intern Med 2003; 254: 132–139. Objective. Fibrinogen is an established predictor of cardiovascular events in the general population but the relationship between fibrinogen, mortality and incident cardiovascular complications has been very little investigated in patients with end-stage renal disease (ESRD). Design and subjects. We investigated the relationship between fibrinogen and all cause mortality and cardiovascular outcomes in a prospective cohort study in 192 patients on chronic haemodialysis treatment (follow-up: 34 ± 16 months). Results. Fibrinogen was significantly higher in patients who died during the follow-up than in those who survived. Similarly, fibrinogen was higher in patients who had fatal or nonfatal cardiovascular events than in event free patients. On multivariate Cox regression analysis fibrinogen was an independent predictor of survival [hazard ratio (1 g L−1 increase in plasma fibrinogen): 1.19, 95% confidence interval (CI): 1.05–1.35, P = 0.006] and a highly significant (P = 0.0008), independent predictor of fatal and nonfatal cardiovascular events [hazard ratio (1 g L−1 increase in plasma fibrinogen): 1.25, 95% CI: 1.10–1.43] in a model including traditional risk factors and serum C-reactive protein (CRP) and plasma homocysteine. Conclusions. Fibrinogen is as an independent risk factor for overall and cardiovascular mortality in patients with ESRD. Intervention studies are required to see whether reducing plasma fibrinogen may help to curb the exceedingly high cardiovascular risk of the uremic population.

Background We investigated the relationship between fibrinogen and echocardiographic measurements of left ventricular (LV) geometry and LV function in a group of 192 patients with end stage renal disease (ESRD). Results Patients in the third fibrinogen tertile had higher mean wall thickness (MWT), relative wall thickness (RWT) and left ventricular mass index (LVMI) and lower LV end diastolic diameter and LV ejection fraction than those in the other tertiles. On multivariate analysis fibrinogen resulted to be an independent correlate of MWT (P = 0·001) and RWT (P = 0·0001) and the first factor in rank explaining the variance in LV ejection fraction (P = 0·0001). Left ventricular concentric hypertrophy was more prevalent (P = 0·001) in patients in the third fibrinogen tertile (n = 35, 54%) than in those in the second (n = 24, 37%) and first (n = 13, 21%) tertiles. In a multiple logistic regression model patients in the third tertile of fibrinogen had a risk for left ventricular concentric hypertrophy that was 3·56 (95%CI: 1·56–8·14) fold higher than in those in the first tertile (P = 0·003). Conclusions Elevated fibrinogen is independently associated with LV concentric hypertrophy and systolic dysfunction in ESRD patients. These relationships may contribute to the negative prognostic impact of elevated fibrinogen levels in ESRD.

Background — Sympathetic tone is consistently raised in patients with end-stage renal disease (ESRD). We therefore tested the hypothesis that sympathetic activation is associated with mortality and cardiovascular events in a cohort of 228 patients undergoing chronic hemodialysis who did not have congestive heart failure at baseline and who had left ventricular ejection fraction >35%. Methods and Results — The plasma concentration of norepinephrine (NE) was used as a measure of sympathetic activity. Plasma NE exceeded the upper limit of the normal range (cutoff 3.54 nmol/L) in 102 dialysis patients (45%). In a multivariate Cox regression model that included all univariate predictors of death as well as the use of sympathicoplegic agents and β-blockers, plasma NE proved to be an independent predictor of this outcome (hazard ratio [1-nmol/L increase in plasma NE]: 1.07, 95% CI 1.01 to 1.14, P =0.03). Similarly, plasma NE emerged as an independent predictor of fatal and nonfatal cardiovascular events (hazard ratio [1-nmol/L increase in plasma NE] 1.08, 95% CI 1.02 to 1.15, P =0.01) in a model that included previous cardiovascular events, pulse pressure, age, diabetes, smoking, and use of sympathicoplegic agents and β-blockers. The adjusted relative risk for cardiovascular complications in patients with plasma NE >75th percentile was 1.92 (95% CI 1.20 to 3.07) times higher than in those below this threshold ( P =0.006). Conclusions — Sympathetic nerve overactivity is associated with mortality and cardiovascular outcomes in ESRD. Controlled trials with antiadrenergic drugs are needed to determine whether interference with the sympathetic system could reduce the high cardiovascular morbidity and mortality in dialysis patients.

non disponibile

Importance: The finding that aortic pulse wave velocity (aPWV) is increased may explain why patients with inflammatory bowel disease (IBD) have an increased cardiovascular risk despite the low prevalence of classic cardiovascular risk factors. Objective: To determine why these patients have an increased aPWV. Data sources: A systematic literature search for aPWV in IBD was performed using PubMed, Scopus, Web of Science, and Google Scholar databases. Study selection: Inclusion criterion was peer-reviewed publications on clinical studies reporting original data. Data extraction and synthesis: This study followed PRISMA-IPD 2015 guidelines. Data were provided for 4 cohorts in 3 countries (151 participants with ulcerative colitis [UC], 159 with Crohn disease [CD], and 227 controls). Using aPWV, cohort-specific z-scores were calculated after loge-transform and combined in meta-analysis to form pooled effects using a random- effects model. Main outcome and measures: The aPWV, a reference measure of aortic stiffness, after adjusting for age, sex, mean blood pressure, known cardiovascular risk factors, and study of origin. Results: The pooled z-score was 1.2 m/s. The aPWV was dependent on CD (β 0.80 z-score [1.0 m/s], 95% confidence interval 0.61–1.00 z-score, P < 0.001) and UC (β 0.69 z- score [0.8 m/s], 95% confidence interval 0.49–0.88 z-score, P < 0.001). In patients with IBD, the aPWV was dependent on disease duration (square root [years], β 0.15 z- score, 95% confidence interval 0.02–0.29 z-score, P = 0.03) and white blood cell count (Loge [billion cells/L], β 0.48 z-score, 95% confidence interval 0.12–0.84 z-score, P = 0.01) but not on cardiovascular risk factors and therapy. Conclusions: The increased aPWV reported in this patient population is dependent on inflammation.

Background The dialysis delivered after a chronic kidney disease (CDK) or any otherwise severe end-stage renal failure is a complex medical task, leading to major medical and psychopathological distress for the patient. The aim of the present study was to analyze the impact of the dialysis experience on the nephrologic patient's global quality of life. Methods In the present cross-sectional study, involving 96 patients with end-stage renal disease receiving hemodialysis, demographic, medical, and psychological differential features across different CDK diagnoses were accounted and were then correlated each other. Results Among other differential features, the “acknowledgement of dependence” (from the medical device delivering the dialysis) emerged as a factor correlated to “self-sufficiency” in CDK patients receiving hemodialysis. Conclusions Although further, larger-sampled studies on the topic are needed, medical and psychological interventions are useful to ensure a better global quality of life and good therapeutic adherence in dialysis patients.

In renal diagnosis, the B-mode ultrasound is used to provide an accurate study of the renal morphology, whereas the colour and power Doppler are of strategic importance in providing qualitative and quantitative information about the renal vasculature, which can also be obtained through the assessment of the resistive index (RI). To date, this is one of the most sensitive parameters in the study of kidney diseases and allows us to quantify the changes in renal plasma flow. If a proper Doppler ultrasound examination is carried out and a critical analysis of the values obtained is performed, the RI measurement at the interlobar artery level has been suggested in the differential diagnosis between nephropathies. The aim of this review is to highlight the pathological conditions in which the study of intrarenal RI provides useful information about the pathophysiology of renal diseases in both the native and the transplanted kidneys.