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IN-HOSPITAL ACUTE KIDNEY INJURY: STUDY OF PREVALENCE, SEX DIFFERECES AND MORTALITY.
No full textBackground:
Hospital Acute kidney injury (H-AKI) is a complex entity associated with an increased risk of complications and mortality. Its occurrence and outcome are influenced by several patient and organizational-related factors. Due to the biological and genetic differences, sex may greatly influence the kidney function. However, Italian epidemiological data on H-AKI incidence and prognosis are scarce. Moreover, the impact of sex on H-AKI risk and related consequences is still unclear.
This retrospective multi-center study aimed to assess H-AKI epidemiology and outcomes in a large cohort of hospitalized patients, with a focus on the association with patients' sex.
Method:
From adult patients admitted to two large University Hospitals in Italy between 2016 and 2019, we collected clinical data, serum creatinine (sCr), comorbidities, with focus on diabetes mellitus (DM), heart failure (HF), sepsis, kidney transplantation and chronic kidney disease (CKD), primary diagnoses as codified in the hospital discharge form (HDF), and data on discharge, length of hospital stay (LOS), and death.
The inclusion criteria were: age >18 years, first hospital admission from January 1, 2016, to December 31, 2019, at least two values of sCr collected during hospitalization. The only exclusion criteria was (CKD) stage 5 reported on HDF.
We defined and graded AKI according to the KDIGO criteria, by comparing the peak sCr to the lowest sCr during hospitalization under the assumption that the lowest sCr would represent baseline kidney function. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration creatinine-based equation.
Results:
We analyzed 87,087 patients, with an average age of 69.2±17.7 years of whom 43467 (49.9%) were males and 43620 females (50.1%). Overall, 17946 patients (20.6%) developed H-AKI, with a higher incidence in females (21.4% vs. 19.8%, p=0.000).
In respect to the non-AKI population, patients with AKI were significantly older (66.7±18.1 vs 74.8±14.7), with a higher prevalence of females (52.1%) and more comorbid conditions, as diabetes mellitus, heart failure, sepsis and CKD.
The logistic regression analysis showed that the risk of AKI was associated to admission sCr (OR 1.55, 95% CI 1.53 -1.58), female gender (OR 1.23, 95% CI 1.18 – 1.27), LOS (OR 1.05, 95% CI 1.05– 1.06) and ICU stay (OR 4.73, 95% CI 4.4– 5.1) in a multivariate model (p<0.0001).
AKI patients had worst outcomes considering mortality (17.7% vs 4.3%), LOS (19.2±16 vs 8.9±11.12), ICU admission (8.2% vs 2,4%) and need for protected discharge (30.0% vs 17.7%). At Cox-analysis AKI resulted related to mortality with a hazard ration of 1.23 (IC 1.16-1.30). The distribution of AKI stages was AKI-1 59.5%, AKI-2 25.7% and AKI-3 14%. The higher stages, as expected, presented the worst outcomes and higher sCr values at discharge.
Female patients were older than males (69.9±16.5 vs 68.5±18.9 years, p<0.001), had less prevalence of DM (8.7% vs 11.8%) and CKD (6% vs 7,7%), and higher prevalence of HF (9.3% vs 8.6). Females with H-AKI were older and exhibited more heart failure, while males presented more acute myocardial ischemia and sepsis. The male/female ratio varied across AKI severity, with stage 3 AKI more frequent in males.
AKI awareness, as evaluated by comparing the incidence of AKI diagnosed according to the sCr changes with AKI diagnoses codified on HDF, showed a higher rate of undetection in females (3.8% vs 4.4%). Moreover, when we stratified our cohort according to the age quartiles, we observed that for each AKI stage in the 1st age quartile H-AKI incidence was higher in males (13.1% vs 10%, p=0.000), in the second quartile there was no difference between male and female patients, while in the last quartiles, AKI incidence was higher in females (25.2 vs 22.6%, p=0.000).
This tendency was also confirmed by Kaplan Meier analysis. However, when we separately analyzed the risk of developing AKI in the different quartiles with multivariate logistic regression analysis we found that while in the youngest quartiles the risk of developing AKI was not correlated with sex, in the elderly, female sex was an independent risk factor for developing AKI (3rd quartile OR 1.30, IC 1.21-1.39; 4th quartile OR 1.46 IC 1.38-1.59, adjusted for age, DM, HF, CKD, admission to ICU, sCr, LOS).
The analysis of outcomes among AKI patients divided between males and females showed that mortality was the same for the youngest patients, while it was higher in male patients for the 3rd and 4th age quartile. A similar trend was found for ICU admission and LOS.
Conclusion:
The study of epidemiological data is crucial to plan preventing and monitoring actions with the aim to improve the in-hospital morbidity and mortality, but also the long-term effects as the progression to CKD.
Sex emerges as a significant determinant of H-AKI development. However, the relationship between sex and H-AKI is not linear. Indeed, AKI incidence, severity, and outcomes vary between males and females across different age groups, probably reflecting the modifications of health status occurring during a lifetime.
Consideration also of gender differences is crucial in studying AKI to ensure accurate and equitable diagnosis and management.
The examination of several factor can lead to enhance strategies to identify the patients at higher risk and focus on them to a more rigorous treatment and monitoring
Microalbuminuria in primary hypertension: a guide to optimal patient management?
No full textAccurate assessment of the global risk profile is considered a prerequisite for the optimal management of hypertensive patients. In particular, the evaluation of subclinical organ damage, namely left ventricular hypertrophy, peripheral atherosclerosis and renal function, plays a key role in optimizing therapeutic targets and strategy in individual patients. Urine albumin excretion is a low-cost, easy-to-use test and a powerful predictor of cardiovascular diseases. The search for albuminuria has, therefore, become routine in the evaluation of hypertensive patients. Moreover, albuminuria has been shown to be associated with early signs of extra-renal organ damage such as left ventricular hypertrophy, and carotid atherosclerosis. Under effective antihypertensive treatment, changes in subclinical organ damage over time, especially regression of left ventricular hypertrophy, are paralleled by modification of risk status and may serve as intermediate endpoints for treatment. More recently, changes in albuminuria have also been proposed to reflect changes in the risk of cardiovascular events. If this is confirmed by large well-designed studies, microalbuminuria may not simply be regarded as a risk predictor but become itself an independent target for treatment
Renin–angiotensin–aldosterone system blockade in chronic kidney disease: current strategies and a look ahead
No full textThe Renin–Angiotensin–Aldosterone System (RAAS) is profoundly involved in the pathogenesis of renal and cardiovascular organ damage, and has been the preferred therapeutic target for renal protection for over 30 years. Monotherapy with either an Angiotensin Converting Enzime Inhibitor (ACE-I) or an Angiotensin Receptor Blocker (ARB), together with optimal blood pressure control, remains the mainstay treatment for retarding the progression toward end-stage renal disease. Combining ACE-Is and ARBs, or either one with an Aldosterone Receptor Antagonist (ARA), has been shown to provide greater albuminuria reduction, and to possibly improve renal outcome, but at an increased risk of potentially severe side effects. Moreover, combination therapy has failed to provide additional cardiovascular protection, and large prospective trials on hard renal endpoints are lacking. Therefore this treatment should, at present, be limited to selected patients with residual proteinuria and high renal risk. Future studies with novel agents, which directly act on the RAAS at multiple levels or have a more favourable side effect profile, are greatly needed to further explore and define the potential for and the limitations of profound pharmacologic RAAS inhibition
The uric acid cardio-nephropathy - La cardionefropatia da acido urico
No full textL’acido urico è un prodotto del catabolismo delle purine che si forma grazie all’enzima xantina-ossidasi
ed è eliminato prevalentemente a livello renale. L’urato può avere un effetto sia anti- che
pro-ossidante a seconda delle diverse condizioni biologiche e dei cofattori presenti. Nuove evidenze
suggeriscono che l’iperuricemia lieve asintomatica può avere un ruolo nello sviluppo di ipertensione,
malattia renale e rischio cardiovascolare. I meccanismi patogenetici alla base della relazione
tra acido urico e danno vascolare sono molteplici. L’aumento dei livelli di acido urico può indurre
disfunzione endoteliale, stress ossidativo con riduzione della produzione di ossido nitrico e vasocostrizione,
stimolare i processi infiammatori e l’attività del sistema renina-angiotensina.Questi meccanismi
agiscono a livello delle cellule endoteliali, dei vasi renali, delle cellule tubulari e dei cardiomiociti,
portando allo sviluppo di ipertensione, aterosclerosi e disfunzione miocardica. Attualmente,
l’acido urico non è più considerato uno spettatore “innocente” ma piuttosto un possibile fattore di
rischio per lo sviluppo di patologie renali e cardiovascolari. È stato infatti dimostrato che l’iperuricemia,
anche moderata, è associata allo sviluppo ed alla progressione di malattia renale cronica ed
ipertensione arteriosa. Studi preliminari sembrano suggerire che la riduzione dell’iperuricemia con
farmaci inibitori della xantina-ossidasi possa portare benefici in termini di mortalità cardiovascolare
e renale. I numerosi trial attualmente in corso, soprattutto con allopurinolo e febuxostat potranno
chiarire questo aspetto.Uric acid is a product of purine catabolism formed by the activity of xanthine-oxidase and prevalently excreted by the kidney. In vivo, urate is known to have both an anti- or pro-oxidant role depending on several biological conditions. New evidence suggests that chronic hyperuricemia can contribute to hypertension development, kidney disease and cardiovascular risk. The pathophysiologic mechanisms are various, such as endothelial dysfunction and oxidative stress, vasoconstriction and stimulation of renin angiotensin system. These processes act at the kidney level, within arterioles and tubular cells, as well as at the systemic vasculature and tissue level causing hypertension, atherosclerosis and myocardial dysfunction. In recent years evidence has grown that asymptomatic hyperuricemia is a possible risk factor for the development of hypertension, diabetes as well as renal and cardiovascular events. Preliminary clinical evidence suggests that lowering uric acid levels by the use of xanthine-oxidase inhibitors may improve cardiovascular and renal risk. Several ongoing trials, both with allopurinol and febuxostat, will clarify this issue in the upcoming years
Biopsy-proven acute tubulointerstitial nephritis in patients treated with immune checkpoint inhibitors: a pooled analysis of case reports
No full textIntroduction: Acute kidney injury (AKI) in cancer patients receiving immune checkpoint inhibitors (ICIs) may recognize multiple causes. Here, we reviewed cases of biopsy-proven acute tubulointerstitial nephritis (ATIN) to describe the clinical characteristics and outcomes of this condition. Method: We conducted a pooled analysis of clinical cases of ICI-related biopsy-proven ATIN up to 1 May 2022. We collected data on clinical characteristics, AKI, biopsy findings, laboratory examinations, and renal outcomes. Results: Eighty-five patients (61.4 ± 19 years, 56 male) were evaluated. Melanoma was the most prevalent diagnosis (51%), followed by non-small cell lung cancer (30%). ICI treatment consisted of PD-1, PDL-1 (nivolumab, pembrolizumab, atezolizumab), and CTLA-4 inhibitors (i) (ipilimumab) or combination PD-1i+CTLA4i. Renal toxicity developed after a median of four cycles of therapy. Fifty-one patients (65.5%) developed the most severe form of AKI- stage 3, including five patients requiring dialysis. All the 19 patients treated with dual ICI blockade developed AKI-stage 3, compared with 29 patients out of the 60 receiving a single agent (p<0.001). Most events were managed with corticosteroids associated with ICI withdrawal. In 15 patients ICI was restarted, but in six (40%) AKI recurred. Overall, 32 patients (40%) presented a complete renal recovery, which chance was inversely associated with dual ICI blockade (OR 0.15, 95CI 0.03-0.7, p=0.01). Conclusion: ICI-related ATIN may develop late after the therapy initiation, presenting as severe AKI, particularly in patients with dual ICI blockade. Although this complication may be partially reversible, concerns remain about the renal function sequelae and the possibility of restarting ICI treatment
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
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
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