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Now showing items 1 - 14 of 14

  • Anti-fibrotic treatments: A review of clinical evidence.

    Allinovi, Marco   De Chiara, Letizia   Angelotti, Maria Lucia   Becherucci, Francesca   Romagnani, Paola  

    Renal fibrosis is a condition characterized by excessive extracellular matrix accumulation in the kidney. Representing the final common result of a variety of injuries, it can lead to chronic kidney disease and end-stage renal disease. Although major efforts have been made in understanding the process of renal fibrosis, attempts to halt its progression have been successful only in a laboratory setting with limited success in clinical practice. Here, we review the current knowledge on the process of renal fibrogenesis and the emerging anti-fibrotic drugs that have shown encouraging results in experimental models and were subsequently tested in clinical trials. We also propose possible explanations that may account for clinical trial failures and poor translation outcomes. Finally, we discuss alternative therapeutic options and future directions in which anti-fibrotic treatments may be coupled with drugs that can enhance endogenous tissue regeneration. Copyright =C2=A9 2018 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.
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  • Anti-fibrotic treatments: A review of clinical evidence

    Allinovi, Marco   De Chiara, Letizia   Angelotti, Maria Lucia   Becherucci, Francesca   Romagnani, Paola  

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  • Line Detection as an Inverse Problem:Application to Lung Ultrasound Imaging

    Anantrasirichai, Nantheera   Hayes, Wesley   Allinovi, Marco   Bull, David   Achim, Alin  

    This paper presents a novel method for line restoration in speckle images. We address this as a sparse estimation problem using both convex and non-convex optimization techniques based on the Radon transform and sparsity regularization. This breaks into subproblems, which are solved using the alternating direction method of multipliers, thereby achieving line detection and deconvolution simultaneously. We include an additional deblurring step in the Radon domain via a total variation blind deconvolution to enhance line visualization and to improve line recognition. We evaluate our approach on a real clinical application: the identification of B-lines in lung ultrasound images. Thus, an automatic B-line identification method is proposed, using a simple local maxima technique in the Radon transform domain, associated with known clinical definitions of line artefacts. Using all initially detected lines as a starting point, our approach then differentiates between B-lines and other lines of no clinical significance, including Z-lines and A-lines. We evaluated our techniques using as ground truth lines identified visually by clinical experts. The proposed approach achieves the best B-line detection performance as measured by the F score when a non-convex l(p) regularization is employed for both line detection and deconvolution. The F scores as well as the receiver operating characteristic (ROC) curves show that the proposed approach outperforms the state-of-the-art methods with improvements in B-line detection performance of 54%, 40%, and 33% for F-0.5, F-1, and F-2, respectively, and of 24% based on ROC curve evaluations.
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  • Structured clinical follow-up for CKD stage 5 may safely postpone dialysis.

    Dattolo, Pietro   Michelassi, Stefano   Amidone, Marco   Allinovi, Marco   Vignali, Lorenzo   Antognoli, Giulia   Roperto, Rosa   Pizzarelli, Francesco  

    BACKGROUND AND OBJECTIVES: The optimal timing of dialysis initiation is still unclear. We aimed to ascertain whether a strict clinical follow-up can postpone need for dialysis in chronic kidney disease (CKD) stage 5 patients.; DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: We reviewed records of all consecutive adult patients attending our conservative CKD stage 5 outpatient clinic from 2001 to 2010. Chronicity was defined as two consecutive estimated glomerular filtration rate (eGFR) measurements below 15 ml/min/1.73 m(2). Characteristics of subjects, including comorbidities, were assessed at baseline; blood pressure and serum markers of uremia were assessed both at first and last visit. GFR was estimated by the 4-variable Modification of Diet in Renal Disease (MDRD) formula.; RESULTS: In the 312 patients analyzed baseline eGFR was 9.7 =C2=B1 2.7 ml/min, which declined by 1.93 =C2=B1 4.56 ml/min after 15.6 =C2=B1 18.2 months. Age was inversely related to eGFR decline (r -0.27, p =3D 0.000). During conservative follow-up 55 subjects (18%) died. In comparison with those eventually entering dialysis, deceased subjects were older and had a longer follow-up with no CKD progression. Multivariate analysis identified age, proteinuria and lower baseline K values as the only independent determinants of death. One hundred ninety-four subjects (66%) started dialysis with an average eGFR of 6.1 =C2=B1 1.9 ml/min. During 35.8 =C2=B1 24.7 months of dialysis follow-up, 84 patients died. Multivariate analysis identified age as the main determinant of death (hazard ratio [HR] for every year 1.07, 95% confidence interval [CI] 1.04-1.11, p 0.000). Patients starting dialysis with eGFR below the median, e.g. <5.7 ml/min, showed a better survival (HR for mortality 0.52, 95% CI 0.30-0.89, p 0.016) than the other group.; CONCLUSIONS: A well-organized nephrological outpatient clinic for conservative follow-up of CKD stage five patients can delay dialysis entry as long as 1 year. Starting dialysis with eGFR lower than 6 ml/min does not confer any increased risk of death in selected early-referral patients.=20
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  • Finding covert fluid:methods for detecting volume overload in children on dialysis

    Allinovi, Marco   Saleem, Moin A.   Burgess, Owen   Armstrong, Catherine   Hayes, Wesley  

    Lung ultrasound is a novel technique for detecting generalized fluid overload in children and adults with end-stage renal disease (ESRD). Echocardiography and bioimpedance spectroscopy are established methods, albeit variably adopted in clinical practice. We compared the practicality and accuracy of lung ultrasound with current objective techniques for detecting fluid overload in children with ESRD. A prospective observational study was performed to compare lung ultrasound B-lines, echocardiographic measurement of inferior vena cava parameters and bioimpedance spectroscopy in the assessment of fluid overload in children with ESRD on dialysis. The utility of each technique in predicting fluid overload, based on short-term weight gain, was assessed. Multiple linear regression models to predict fluid overload by weight were explored. A total of 22 fluid assessments were performed in 13 children (8 on peritoneal dialysis, 5 on haemodialysis) with a median age of 4.0 (range 0.8-14.0) years. A significant linear correlation was observed between the number of B-lines detected by lung ultrasound and fluid overload by weight (r =3D 0.57, p =3D 0.005). A non-significant positive linear correlation was observed between fluid overload by weight and bioimpedance spectroscopy (r =3D 0.43, p =3D 0.2), systolic blood pressure (r =3D 0.19, p =3D 0.4) and physical examination measurements (r =3D 0.19, p =3D 0.4), while a non-significant negative linear relationship was found between the inferior vena cava collapsibility index and fluid overload by weight (r =3D -0.24, p =3D 0.3). In multiple linear regression models, a combination of three fluid parameters, namely lung ultrasound B-lines, clinical examination and systolic blood pressure, best predicted fluid overload (R (2) =3D 0.46, p =3D 0.05). Lung ultrasound may be superior to echocardiographic methods and bioimpedance spectroscopy in detecting volume overload in children with ESRD. Given the practicality and sensitivity of this new technique, it can be adopted alongside clinical examination and blood pressure in the routine assessment of fluid status in children with ESRD.
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  • Finding covert fluid: methods for detecting volume overload in children on dialysis

    Allinovi, Marco   Saleem, Moin A   Burgess, Owen   Armstrong, Catherine   Hayes, Wesley  

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  • Lung ultrasound:a novel technique for detecting fluid overload in children on dialysis

    Allinovi, Marco   Saleem, Moin   Romagnani, Paola   Nazerian, Peiman   Hayes, Wesley  

    Background: Optimizing the target weight of infants and children on dialysis remains an important clinical challenge. The use of ultrasound to detect fluid overload in adult patients on dialysis is receiving growing attention. We hypothesized that fluid overload can be quantified in infants and children receiving dialysis using lung ultrasound. Methods: In this prospective observational study, infants and children receiving dialysis for end-stage renal disease (ESRD) or acute kidney injury (AKI) in a regional paediatric nephrology centre were eligible. Lung ultrasound examinations were performed during in-centre dialysis, on home visits or in an outpatient clinic. Fluid overload was assessed by quantifying B-lines on ultrasound and compared with proportional (%) increase in patient weight from the target weight. Results: A total of 142 ultrasound assessments were performed in 23 children. In children with AKI, median B-line score reduced from 5 (range 0-22) at presentation to 1.5 (0-4) at recovery (P =3D 0.04) with concurrent improvement in fluid overload judged by weight from 7.2 (- 1.9 to 15.2)% to 0%. A linear correlation between lung ultrasound B-line score and fluid overload judged by weight was observed in children with AKI (r =3D 0.83) and ESRD (r =3D 0.61). Inter-observer variability was acceptable. Conclusions: Lung ultrasound is a practical and sensitive method of quantifying subclinical fluid overload in infants and children on dialysis. Interventional studies to determine the benefits of using lung ultrasound to optimize the target weight for children with ESRD are merited.
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  • Lung ultrasound: a novel technique for detecting fluid overload in children on dialysis

    Allinovi, Marco   Saleem, Moin   Romagnani, Paola   Nazerian, Peiman   Hayes, Wesley  

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  • Acute kidney injury promotes development of papillary renal cell adenoma and carcinoma from renal progenitor cells

    Peired, Anna Julie   Antonelli, Giulia   Angelotti, Maria Lucia   Allinovi, Marco   Guzzi, Francesco   Sisti, Alessandro   Semeraro, Roberto   Conte, Carolina   Mazzinghi, Benedetta   Nardi, Sara   Melica, Maria Elena   De Chiara, Letizia   Lazzeri, Elena   Lasagni, Laura   Lottini, Tiziano   Landini, Samuela   Giglio, Sabrina   Mari, Andrea   Di Maida, Fabrizio   Antonelli, Alessandro   Porpiglia, Francesco   Schiavina, Riccardo   Ficarra, Vincenzo   Facchiano, Davide   Gacci, Mauro   Serni, Sergio   Carini, Marco   Netto, George J.   Roperto, Rosa Maria   Magi, Alberto   Christiansen, Christian Fynbo   Rotondi, Mario   Liapis, Helen   Anders, Hans-Joachim   Minervini, Andrea   Raspollini, Maria Rosaria   Romagnani, Paola  

    Acute tissue injury causes DNA damage and repair processes involving increased cell mitosis and polyploidization, leading to cell function alterations that may potentially drive cancer development. Here, we show that acute kidney injury (AKI) increased the risk for papillary renal cell carcinoma (pRCC) development and tumor relapse in humans as confirmed by data collected from several single-center and multicentric studies. Lineage tracing of tubular epithelial cells (TECs) after AKI induction and long-term follow-up in mice showed time-dependent onset of clonal papillary tumors in an adenoma-carcinoma sequence. Among AKI-related pathways, NOTCH1 overexpression in human pRCC associated with worse outcome and was specific for type 2 pRCC. Mice overexpressing NOTCH1 in TECs developed papillary adenomas and type 2 pRCCs, and AKI accelerated this process. Lineage tracing in mice identified single renal progenitors as the cell of origin of papillary tumors. Single-cell RNA sequencing showed that human renal progenitor transcriptome showed similarities to PT1, the putative cell of origin of human pRCC. Furthermore, NOTCH1 overexpression in cultured human renal progenitor cells induced tumor-like 3D growth. Thus, AKI can drive tumorigenesis from local tissue progenitor cells. In particular, we find that AKI promotes the development of pRCC from single progenitors through a classical adenoma-carcinoma sequence.
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  • Biomarkers and Prediction of Prognosis in Transthyretin-Related Cardiac Amyloidosis:Direct Comparison of Two Staging Systems

    Cappelli, Francesco   Martone, Raffaele   Gabriele, Martina   Taborchi, Giulia   Morini, Sofia   Vignini, Elisa   Allinovi, Marco   Di Gioia, Massimo   Bartolini, Simone   Di Mario, Carlo   Perfetto, Federico  

    Background: The severity of heart disease varies widely among patients with transthyretin-related cardiac amyloidosis (ATTR-CA) at presentation, and availability of tools able to predict prognosis is essential for clinical and research purposes. Currently, two biomarker-based staging systems are available. The aim of this study was to compare their predictive performance. Methods: A total of 175 patients diagnosed with ATTR-CA (133 wild-type and 42 hereditary) were stratified into different stages based on 2 systems: the first system included N-terminal pro-B-type natriuretic peptide (NT-proBNP) and estimated glomerular filtration rate (eGFR), and the second one included NT-proBNP and troponin I (TnI). Survival estimates and age-adjusted survival for all-cause mortality were analysed over a median follow-up of 27 months (interquartile range 16-43 months). Results: Predictive performance was more accurate when NT-proBNP and eGFR were used, resulting in effective survival stratification: 64.4 months for stage 1, 44.6 months for stage 2, and 20.5 months for stage 3 (P < 0.01 for stages 1 vs 2; P < 0.0001 for stages 1 vs 3; P < 0.0001 stages 2 vs 3). The combination of NT-proBNP and TnI was unable to effectively differentiate survival: 64.5 months for stage 1, 50.9 months for stage 2, and 27.3 months for stage 3 (P =3D 0.223 for stages 1 vs 2; P < 0.0001 for stages 1 vs 3; P < 0.0001 for stages 2 vs 3). The same results were seen after age adjustment. Conclusions: A staging system using NT-proBNP and eGFR had better prognostic accuracy for ATTR-CA patients compared with one using NTproBNP and TnI.
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  • Thrombotic microangiopathy induced by interferon beta in patients with multiple sclerosis:three cases treated with eculizumab

    Allinovi, Marco   Cirami, Calogero Lino   Caroti, Leonardo   Antognoli, Giulia   Farsetti, Silvia   Amato, Maria Pia   Minetti, Enrico Eugenio  

    Background: Interferon-beta (IFN-beta) is one of the most widely prescribed medications for relapsing-remitting multiple sclerosis (RRMS). IFN-related thrombotic microangiopathy (TMA) is a rare but severe complication, with a fulminant clinical onset and a possibly life-threatening outcome that may occur years after a well-tolerated treatment with IFN. Most patients evolve rapidly to advanced chronic kidney disease and eventually to renal failure. Methods: We performed a retrospective analysis of TMA cases diagnosed and managed in our Nephrology Department from 2010 to 2015, and performed a literature review of IFN-beta-induced TMA. Results: Three cases of TMA among patients treated with IFN-beta were identified who did not show any renal improvement following conventional therapy: IFN withdrawal and plasma exchange (PE, range 8-18) sessions. All of them responded favourably to eculizumab, with progressive clinical and renal improvement, allowing dialysis discontinuation, without recurrence of TMA during a long-term follow-up (range 1-5 years). Conclusions: TMA is a recognized severe complication in RRMS patients treated with IFN-beta. Withdrawal of IFN and treatment with PE, steroids or rituximab did not improve the poor renal prognosis in our three patients and in all the previously described cases in the literature. In our experience, eculizumab had a strikingly favourable effect on renal recovery, suggesting a role of IFN-beta as a trigger in complement-mediated TMA. Neurologists and nephrologists should be vigilant to this complication to prevent possibly irreversible renal damage.
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  • Association of Serum C3 Concentration and Histologic Signs of Thrombotic Microangiopathy with Outcomes among Patients with ANCA-Associated Renal Vasculitis.

    Manenti, Lucio   Vaglio, Augusto   Gnappi, Elisa   Maggiore, Umberto   Allegri, Landino   Allinovi, Marco   Urban, Maria L   Delsante, Marco   Galetti, Maricla   Nicastro, Maria   Pilato, Francesco P   Buzio, Carlo  

    BACKGROUND AND OBJECTIVES: Complement alternative pathway (cAP) activation has recently been recognized as a key pathogenic event in ANCA-associated vasculitis (AAV). cAP dysregulation is also a major determinant of thrombotic microangiopathies (TMA), which can in turn complicate AAV. We explored the prognostic significance of cAP activation and of histologic evidence of TMA in a cohort of patients with renal AAV.; DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We studied 46 patients with AAV diagnosed between January 1990 and December 2011 at the Nephrology Unit of Parma University Hospital; 30 of them had undergone renal biopsy. We analyzed serum levels of C3 (sC3) and C4 (sC4) and, for 19 patients who had frozen plasma, plasma Bb and C5b-9 levels. We also reviewed all kidney biopsy specimens, specifically searching for histologic signs of TMA, and performed immunofluorescence or immunohistochemistry for C3d, C4d, Bb and C5b-9.; RESULTS: sC3 was below the lower limit of normal in 35% of the patients, whereas C4 was low in only 2%. Patients with low sC3 tended to be older (P=3D0.04) and to have lower eGFR at diagnosis (P=3D0.06). The median follow-up was 78 months (interquartile range, 18-135 months); 18 patients reached ESRD (10 of 14 and 8 of 26 in the low and normal sC3 groups, respectively). Death-censored renal survival was lower in the low sC3 group than in the normal sC3 group (log-rank test, P=3D0.01). Eight of the 30 patients who had undergone biopsy (27%) had histologic signs of TMA; these signs were more frequent in patients with low sC3 (5 of 10 versus 3 of 20; P=3D0.04). Notably, patients with histologic signs of TMA had a dramatically worse death-censored renal survival than patients without TMA (log-rank test, P=3D0.01), with ESRD occurring in 8 of 8 patients with TMA versus 8 of 22 patients without TMA.; CONCLUSIONS: Low sC3 levels and histologic signs of TMA are associated with a poor renal prognosis in patients with AAV. Copyright =C2=A9 2015 by the American Society of Nephrology.
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  • The Predictive Role of Biomarkers for the Detection of Acute Kidney Injury After Partial or Radical Nephrectomy:A Systematic Review of the Literature

    Antonelli, Alessandro   Allinovi, Marco   Cocci, Andrea   Russo, Giorgio Ivan   Schiavina, Riccardo   Rocco, Bernardo   Giovannalberto, Pini   Celia, Antonio   Galfano, Antonio   Varca, Virginia   Bozzini, Giorgio   Ceruti, Carlo   Greco, Francesco   Verze, Paolo   Pastore, Antonio Luigi   Porreca, Angelo   Minervini, Andrea  

    Context: Postoperative acute kidney injury (AKI) is a serious complication after kidney surgery, associated with prolonged hospital stay, high morbidity, and mortality. Biomarkers represent a tool of increasing importance to identify renal impairment after partial nephrectomy(PN) or radical nephrectomy (RN) in order to optimize and anticipate the diagnosis of AKI. Objective: The goal of this systematic review is to investigate current insights on the role of biomarkers in predicting renal impairment in patients undergoing PN or RN. Evidence acquisition: A systematic review was conducted up to November 30, 2017 through PubMed, Scopus, and Embase databases, to identify eligible studies evaluating the role of biomarkers for the prediction ofAKI after PN or RN. The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) criteria were applied to select articles. Evidence synthesis: According to the study selection criteria, 10 publications were included with a total number of 728 patients. Incidence of AKI was 26.7% (range: 9-58%). Based on the evidence reviewed, serum cystatin C and urinary neutrophil gelatinase-associated lipocalin (NGAL) showed a significant correlation with serum creatinine rise postoperatively, emerging as potential noninvasive and early biomarkers of AKI in patients undergoing renal surgery. In this setting, serum cystatin C and urinary NGAL have preceded the rise in serum creatinine peak from 3 up to 24 h, even in case of mild renal damage. Conclusions: The literature underlines the potential usefulness of biomarkers such as cystatin C and NGAL as promising and early tools to predict AKI after PN or RN. However, no strong evidence in support of their use is available to date and further investigations are awaited. Patient summary: We looked at the role of biomarkers in predicting renal injury in patients undergoing partial or radical nephrectomy. Serum cystatin C and urinary neutrophil gelatinase-associated lipocalin have emerged as promising noninvasive. accurate, and early biomarkers. (C) 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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  • The Predictive Role of Biomarkers for the Detection of Acute Kidney Injury After Partial or Radical Nephrectomy: A Systematic Review of the Literature

    Antonelli, Alessandro   Allinovi, Marco   Cocci, Andrea   Russo, Giorgio Ivan   Schiavina, Riccardo   Rocco, Bernardo   Giovannalberto, Pini   Celia, Antonio   Galfano, Antonio   Varca, Virginia   Bozzini, Giorgio   Ceruti, Carlo   Greco, Francesco   Verze, Paolo   Pastore, Antonio Luigi   Porreca, Angelo   Minervini, Andrea  

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