1,721,016 research outputs found
Aldosterone antagonists for preventing the progression of chronic kidney disease
No full textBackgroundTreatment with angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) is increasingly used to reduce proteinuria and retard the progression of chronic kidney disease (CKD). However, resolution of proteinuria may be incomplete with these therapies and the addition of an aldosterone antagonist may be added to further prevent progression of CKD. This is an update of a review first published in 2009.ObjectivesTo evaluate the effect of aldosterone antagonists (both selective (eplerenone) and non-selective (spironolactone)) alone or in combination with ACEi or ARB in adults who have CKD with proteinuria (nephrotic and non-nephrotic range) on: patient-centred endpoints including major cardiovascular events, hospitalisation and all-cause mortality; kidney function (proteinuria, glomerular filtration rate (GFR), serum creatinine, and need for renal replacement therapy; and adverse events (including gynaecomastia and hyperkalaemia).Search methodsFor this update, we searched the Cochrane Renal Group's Specialised Register to 30 January 2013 using search terms relevant to this review.Selection criteriaWe included randomised controlled trials (RCTs) and quasi-RCTs that compared aldosterone antagonists alone or in combination with ACEi or ARB (or both) with other anti-hypertensive strategies or placebo.Data collection and analysisTwo authors independently assessed study quality and extracted data. Data were summarised using random effects meta-analysis. We tested for heterogeneity in estimated treatment effects using the Cochran Q test and I-2 statistic. We expressed summary treatment estimates as a risk ratio (RR) for dichotomous outcomes together with their 95% confidence intervals (CI) and mean difference (MD) for continuous outcomes, or standardised mean difference (SMD) when different scales were used.Main resultsWe identified 27 studies (1549 participants) that were eligible for inclusion. These studies provided no data relating to aldosterone antagonists in addition to ACEi or ARB (or both) on patient-level outcomes including major cardiovascular events and mortality and progression to end-stage kidney disease (ESKD) requiring dialysis or transplantation.Compared with ACEi or ARB (or both), non-selective aldosterone antagonists (spironolactone) combined with ACEi or ARB (or both) significantly reduced 24-hour protein excretion (11 studies, 596 participants): SMD -0.61, 95% CI -1.08 to -0.13). There was a significant reduction in both systolic and diastolic blood pressure (BP) at the end of treatment with additional non-selective aldosterone antagonist therapy (systolic BP (10 studies, 556 participants): MD -3.44 mm Hg, 95% CI -5.05 to -1.83) (diastolic BP (9 studies, 520 participants): MD -1.73 mm Hg, 95% CI -2.83 to -0.62).However, we found that aldosterone antagonist treatment had imprecise effects at the end of treatment on GFR (9 studies, 528 participants; MD -2.55 mL/min/1.73 m(2), 95% CI -5.67 to 0.51), doubled the risk of hyperkalaemia (11 studies, 632 patients): RR 2.00, 95% CI 1.25 to 3.20; number needed to treat for an additional harmful outcome (NNTH): 7.2, 95% CI 3.4 to) and increased the risk of gynaecomastia compared to ACEi or ARB (or both) (4 studies, 281 patients): RR 5.14, 95% CI 1.14 to 23.23; NNTH: 14.1, 95% CI 8.7 to 37.3).Most studies enrolled few patients (range 12 to 268) and were powered to observe differences in surrogate end points rather than patient-focused outcomes. Nine studies had a cross-over design and the majority of studies did not adequately report study methods to assess methods and study quality.Authors' conclusionsAldosterone antagonists reduced proteinuria and blood pressure in adults who had mild to moderate CKD and were treated with ACEi or ARB (or both), but increase hyperkalaemia and gynaecomastia. Whether adding aldosterone antagonists to ACEi or ARB (or both) reduced the risk of major cardiovascular events or ESKD in this population is unknown
Short-term vascular hemodynamic responses to isometric exercise in young adults and in the elderly
No full textRenee Hartog,1,* Davide Bolignano,1,2,* Eric Sijbrands,1 Giacomo Pucci,3,4 Francesco Mattace-Raso1 1Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands; 2Institute of Clinical Physiology, Italian National Council of Research, Reggio Calabria, Italy; 3Department of Medicine, University of Perugia, Perugia, Italy; 4Unit of Internal Medicine, Terni University Hospital, Terni, Italy *These authors contributed equally to this work Background: Vascular aging is known to induce progressive stiffening of the large elastic arteries, altering vascular hemodynamics under both rest and stress conditions. In this study, we aimed to investigate changes in vascular hemodynamics in response to isometric handgrip exercise across ages.Participants and methods: We included 62 participants, who were divided into three age categories: 20–40 (n=22), 41–60 (n=20), and 61–80 (n=20) years. Vascular hemodynamics were measured using the Mobil-o-Graph® based on the pulsatile pressure changes in the brachial artery. One-way ANOVA test was performed to analyze the changes induced by isometric handgrip exercise.Results: After isometric handgrip exercise, aortic pulse wave velocity (PWV) increased by 0.10 m/s in the youngest, 0.06 m/s in the middle-age, and 0.02 m/s in the oldest age category. Changes in PWV strongly correlated with those in central systolic blood pressure (cSBP) (r=0.878, P<0.01). After isometric exercise, the mean change of systolic blood pressure (SBP) was -1.9% in the youngest, 0.6% in the middle-aged, and 8.2% in the oldest subjects. Increasing handgrip strength was associated with an increase in SBP and cSBP (1.08 and 1.37 mmHg per 1 kg increase in handgrip strength, respectively, P=0.01). Finally, PWV was significantly associated with increasing handgrip strength with an increase of 0.05 m/s per 1 kg higher handgrip strength (P=0.01).Conclusion: This study found increased blood pressure levels after isometric challenge and a strong association between handgrip strength and change in blood pressure levels and aortic stiffness in elderly subjects. Keywords: vascular aging, isometric stress, blood pressure, pulse wave velocity 
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Interventions for preventing the progression of autosomal dominant polycystic kidney disease
No full textBackgroundAutosomal dominant polycystic kidney disease (ADPKD) is themost common inherited disorder causing kidney disease. Current clinical management of ADPKD focuses primarily on symptom control and reducing associated complications, particularly hypertension. In recent years, improved understanding of molecular and cellular mechanisms involved in kidney cyst growth and disease progression has resulted in new pharmaceutical agents to target disease pathogenesis to prevent progressive disease.ObjectivesWe aimed to evaluate the effects of interventions for preventing ADPKD progression on kidney function, kidney endpoints, kidney structure, patient-centred endpoints (such as cardiovascular events, sudden death, all-cause mortality, hospitalisations, BP control, quality of life, and kidney pain), as well as the general and specific adverse effects related to their use.Search methodsWe searched the Cochrane Renal Group's Specialised Register to 6 June 2015 using relevant search terms.Selection criteriaRandomised controlled trials (RCTs) comparing any interventions for preventing the progression of ADPKD with other interventions or placebo were considered for inclusion without language restriction.Data collection and analysisTwo authors independently assessed study risks of bias and extracted data. We summarised treatment effects on clinical outcomes, kidney function and structure and adverse events using random effects meta-analysis. We assessed heterogeneity in estimated treatment effects using the Cochran Q test and I-2 statistic. Summary treatment estimates were calculated as a mean difference (MD) or standardised mean difference (SMD) for continuous outcomes and a risk ratio (RR) for dichotomous outcomes together with their 95% confidence intervals.Main resultsWe included 30 studies (2039 participants) that investigated 11 pharmacological interventions (angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs), calcium channel blockers, beta blockers, vasopressin receptor 2 (V2R) antagonists, mammalian target of rapamycin (mTOR) inhibitors, somatostatin analogues, antiplatelet agents, eicosapentaenoic acids, statins and vitamin D compounds) in this review.ACEi significantly reduced diastolic blood pressure (9 studies, 278 participants: MD -4.96 mm Hg, 95% CI -8.88 to -1.04), but had uncertain effects on kidney volumes (MD -42.50 mL, 95% CI -115.68 to 30.67), GFR (MD -3.41 mL/min/1.73 m(2), 95% CI -15.83 to 9.01), and SCr (MD -0.02 mg/dL, 95% CI -0.14 to 0.09), in data largely restricted to children. ACEi did not show different effects on GFR (MD -8.19 mL/min/1.73 m(2), 95% CI -29.46 to 13.07) and albuminuria (SMD-0.19, 95% CI -1.77 to 1.39) when compared with beta-blockers, or SCr (MD 0.00 mg/dL, 95% CI -0.09 to 0.10) when compared with ARBs.Data for effects of V2R antagonists on kidney function and volumes compared to placebo were limited to narrative information within a single study while these agents increased thirst (1444 participants: RR 2.70, 95% CI 2.24 to 3.24) and dry mouth (1455 participants: RR 1.33, 95% CI 1.01 to 1.76).Compared with no treatment, mTOR inhibitors had uncertain effects on kidney function (2 studies, 115 participants: MD 4.45 mL/min/1.73 m(2), 95% CI -3.20 to 12.11) and kidney volume (MD -0.08 L, 95% CI -0.75 to 0.59) but in three studies (560 participants) caused angioedema (RR 13.39, 95% CI 2.56 to 70.00), oral ulceration (RR 6.77, 95% CI 4.42 to 10.38), infections (RR 1.14, 95% CI 1.04 to 1.25) and diarrhoea (RR 1.70, 95% CI 1.26 to 2.29).Somatostatin analogues (6 studies, 138 participants) slightly improved SCr (MD-0.43 mg/dL,95% CI -0.86 to -0.01) and total kidney volume (MD -0.62 L, 95% CI -1.22 to -0.01) but had no definite effects on GFR (MD 9.50 mL/min, 95% CI -4.45 to 23.44) and caused diarrhoea (RR 3.72, 95% CI 1.43 to 9.68).Data for calcium channel blockers, eicosapentaenoic acids, statins, vitamin D compounds and antiplatelet agents were sparse and inconclusive.Random sequence generation was adequate in eight studies, and in almost half of the studies, blinding was not present or not specified. Most studies did not adequately report outcomes, which adversely affected our ability to assess this bias. The overall drop-out rate was over 10% in nine studies, and few were conducted using intention-to-treat analyses.Authors' conclusionsAlthough several interventions are available for patients with ADPKD, at present there is little or no evidence that treatment improves patient outcomes in this population and is associated with frequent adverse effects. Additional large randomised studies focused on patient-centred outcomes are needed
Unraveling Cardiovascular Risk in Renal Patients: A New Take on Old Tale
No full textChronic kidney disease (CKD), defined by an estimated glomerular filtration rate <60 ml/min/1.73 m2 and/or an increase in urine protein excretion (i.e., albuminuria), is an important public health problem. Prevalence and incidence of CKD have risen by 87 and 89%, worldwide, over the last three decades. The onset of either albuminuria and eGFR reduction has found to predict higher cardiovascular (CV) risk, being this association strong, independent from traditional CV risk factors and reproducible across different setting of patients. Indeed, this relationship is present not only in high risk cohorts of CKD patients under regular nephrology care and in those with hypertension or type 2 diabetes, but also in general, otherwise healthy population. As underlying mechanisms of damage, it has hypothesized and partially proved that eGFR reduction and albuminuria can directly promote endothelial dysfunction, accelerate atherosclerosis and the deleterious effects of hypertension. Moreover, the predictive accuracy of risk prediction models was consistently improved when eGFR and albuminuria have been added to the traditional CV risk factors (i.e., Framingham risk score). These important findings led to consider CKD as an equivalent CV risk. Although it is hard to accept this definition in absence of additional reports from scientific Literature, a great effort has been done to reduce the CV risk in CKD patients. A large number of clinical trials have tested the effect of drugs on CV risk reduction. The targets used in these trials were different, including blood pressure, lipids, albuminuria, inflammation, and glucose. All these trials have determined an overall better control of CV risk, performed by clinicians. However, a non-negligible residual risk is still present and has been attributed to: (1) missed response to study treatment in a consistent portion of patients, (2) role of many CV risk factors in CKD patients not yet completely investigated. These combined observations provide a strong argument that kidney measures should be regularly included in individual prediction models for improving CV risk stratification. Further studies are needed to identify high risk patients and novel therapeutic targets to improve CV protection in CKD patients
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Neutrophil gelatinase-associated lipocalin immunoexpression in renal tumors: correlation with histotype and histological grade
No full textNeutrophil gelatinase-associated lipocalin (NGAL) is a 25 kDa protein with roles in iron trafficking as well as in carcinogenesis and progression of several human neoplasias. Although the renal proximal tubule represents a major source of NGAL synthesis under various injurious stimuli to the kidney, NGAL expression has been rarely evaluated in renal tumors up to now. In view of this, in the present study we analyzed the expression of this protein in renal tumors of different histotype and grade so as to evaluate whether a role for NGAL might be also proposed in the carcinogenesis of these neoplasms. NGAL immunoexpression was analyzed in 30 surgically resected renal tumors [18 clear cell, 5 papillary and 3 chromophobe renal cell carcinomas (RCCs), 2 urothelial carcinomas and 2 oncocytomas] and in the peritoneal metastasis of a clear cell RCC. A variable NGAL immunoexpression was found in 28/30 cases. High NGAL expression was significantly associated with the papillary and chromphobe histotypes (P=0.016) and with a higher histological grade of clear cell and papillary RCC (P=0.004). Moreover, NGAL expression was retained in the peritoneal metastasis of clear cell RCC. Our findings demonstrate that NGAL is expressed in several histotypes of renal tumors. Its highest expression in the papillary and chromophobe histotypes might be related to a higher need in iron uptake, which could be exploited in anti-cancer therapies with iron chelators against these neoplasias. Further studies are required to investigate the potential diagnostic utility of NGAL in the early diagnosis of metastatic progression of RCC
[Italian adaptation of the European Renal Best Practice (ERBP) guideline on kidney donor and recipient evaluation and perioperative care]
No full textRecently, the ERBP (European Renal Best Practice) guideline on kidney donor and recipient evaluation and perioperative care has been published and disseminated to the international nephrology community. This guideline aims at providing evidence-based recommendations on the evaluation of the kidney transplant candidate. They evaluate the immunologic workup of kidney donors and recipients, they recommend the evaluation, selection and preparation of deceased and living kidney donors and the perioperative care of the kidney transplant recipient. We report here the Italian adaptation of these guidelines, with a focus on the main statements elaborated for each single clinical question
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