Evaluation of the genetic risk for COVID-19 outcomes in COPD and differences among worldwide populations.

BACKGROUND: Populations seem to respond differently to the global pandemic of severe acute respiratory syndrome coronavirus 2. Recent studies show individual variability in both susceptibility and clinical response to COVID-19 infection. People with chronic obstructive pulmonary disease (COPD) constitute one of COVID-19 risk groups, being already associated with a poor prognosis upon infection. This study aims contributing to unveil the underlying reasons for such prognosis in people with COPD and the variability in the response observed across worldwide populations, by looking at the genetic background as a possible answer to COVID-19 infection response heterogeneity. METHODS: SNPs already associated with susceptibility to COVID-19 infection (rs286914 and rs12329760) and severe COVID-19 with respiratory failure (rs657152 and rs11385942) were assessed and their allelic frequencies used to calculate the probability of having multiple risk alleles. This was performed on a Portuguese case-control COPD cohort, previously clinically characterized and genotyped from saliva samples, and also on worldwide populations (European, Spanish, Italian, African, American and Asian), using publicly available frequencies data. A polygenic risk analysis was also conducted on the Portuguese COPD cohort for the two mentioned phenotypes, and also for hospitalization and survival to COVID-19 infection. FINDINGS: No differences in genetic risk for COVID-19 susceptibility, hospitalization, severity or survival were found between people with COPD and the control group (all p-values > 0.01), either considering risk alleles individually, allelic combinations or polygenic risk scores. All populations, even those with European ancestry (Portuguese, Spanish and Italian), showed significant differences from the European population in genetic risk for both COVID-19 susceptibility and severity (all p-values < 0.0001). CONCLUSION: Our results indicate a low genetic contribution for COVID-19 infection predisposition or worse outcomes observed in people with COPD. Also, our study unveiled a high genetic heterogeneity across major world populations for the same alleles, even within European sub-populations, demonstrating the need to build a higher resolution European genetic map, so that differences in the distribution of relevant alleles can be easily accessed and used to better manage diseases, ultimately, safeguarding populations with higher genetic predisposition to such diseases.

COPD profiles and treatable traits using minimal resources: identification, decision tree and stability over time.

BACKGROUND AND OBJECTIVE: Profiles of people with chronic obstructive pulmonary disease (COPD) often do not describe treatable traits, lack validation and/or their stability over time is unknown. We aimed to identify COPD profiles and their treatable traits based on simple and meaningful measures; to develop and validate a decision tree and to explore profile stability over time. METHODS: An observational, prospective study was conducted. Clinical characteristics, lung function, symptoms, impact of the disease (COPD Assessment Test-CAT), health-related quality of life, physical activity, lower-limb muscle strength and functional status were collected cross-sectionally and a subsample was followed-up monthly over six months. A principal component analysis and a clustering procedure with k-medoids were applied to identify profiles. A decision tree was developed and validated cross-sectionally. Stability was explored over time with the ratio between the number of timepoints that a participant was classified in the same profile and the total number of timepoints (i.e., 6). RESULTS: 352 people with COPD (67.4 ± 9.9 years; 78.1% male; FEV1 = 56.2 ± 20.6% predicted) participated and 90 (67.6 ± 8.9 years; 85.6% male; FEV1 = 52.1 ± 19.9% predicted) were followed-up. Four profiles were identified with distinct treatable traits. The decision tree included CAT (< 18 or ≥ 18 points); age (< 65 or ≥ 65 years) and FEV1 (< 48 or ≥ 48% predicted) and had an agreement of 71.7% (Cohen's Kappa = 0.62, p < 0.001) with the actual profiles. 48.9% of participants remained in the same profile whilst 51.1% moved between two (47.8%) or three (3.3%) profiles over time. Overall stability was 86.8 ± 15%. CONCLUSION: Four profiles and treatable traits were identified with simple and meaningful measures possibly available in low-resource settings. A decision tree with three commonly used variables in the routine assessment of people with COPD is now available for quick allocation to the identified profiles in clinical practice. Profiles and treatable traits may change over time in people with COPD hence, regular assessments to deliver goal-targeted personalised treatments are needed.

Saliva as a non-invasive specimen for COPD assessment.

BACKGROUND: People with COPD have been reported to bear a distinct airway microbiota from healthy individuals based on bronchoalveolar lavage (BAL) and sputum samples. Unfortunately, the collection of these samples involves relatively invasive procedures and is resource-demanding, limiting its regular use. Non-invasive samples from the upper airways could constitute an interesting alternative, but its relationship with COPD is still underexplored. We examined the merits of saliva to identify the typical profile of COPD oral bacteria and test its association with the disease. METHODS: Outpatients with COPD and age-sex matched healthy controls were recruited and characterised based on clinical parameters and 16S rRNA profiling of oral bacteria. A clustering analysis based on patients' oral bacteria beta-diversity and logistic regressions were performed to evaluate the association between oral bacteria composition and COPD. RESULTS: 128 individuals participated (70 patients and 58 controls). Differential abundance analyses showed differences in patients comparable to the ones previously observed in samples from the lower respiratory tract, i.e., an increase in Proteobacteria (particularly Haemophilus) and loss of microbiota diversity. An unsupervised clustering analysis separated patients in two groups based on microbiota composition differing significantly in the frequency of patients hospitalized due to severe acute exacerbation of COPD (AECOPD) and in the frequency of GOLD D patients. Furthermore, a low frequency of Prevotella was associated with a significantly higher risk of recent severe AECOPD and of being GOLD D. CONCLUSION: Salivary bacteria showed an association with COPD, particularly with severe exacerbations, supporting the use of this non-invasive specimen for future studies of heterogeneous respiratory diseases like COPD.

Construct validity of the brief physical activity assessment tool for clinical use in COPD.

INTRODUCTION: Low physical activity (PA) levels are associated with poor health-related outcomes in Chronic Obstructive Pulmonary Disease (COPD). Thus, PA should be routinely assessed in clinical practice. OBJECTIVES: This study assessed the construct validity of the Brief Physical Activity Assessment Tool (BPAAT) for clinical use in COPD and explored differences in age, sex and COPD grades. METHODS: After linguistic adaptation of the tool to Portuguese, 110 patients (66.4 ± 9.6yrs, 72.7% male, FEV1  = 59.3 ± 25.5%predicted) completed the BPAAT and received an accelerometer. The BPAAT includes two questions assessing the weekly frequency and duration of vigorous- and moderate-intensity PA/walking, classifying individuals as insufficiently or sufficiently active. The BPAAT was correlated with accelerometry (moderate PA, MPA = 1952-5724 counts-per-min [CPM]); vigorous PA, VPA = 5725-∞CPM; moderate-to-vigorous PA, MVPA = 1952-∞CPM; daily steps), through: Spearman's correlations (ρ) for continuous data; %agreement, Kappa, sensitivity and specificity, positive and negative predictive values (PPV, NPV) for categorical data. RESULTS: The BPAAT identified 73.6% patients as "insufficiently active" and 26.4% as "sufficiently active". The BPAAT was weakly to moderately correlated with accelerometry (0.394 ≤ ρ ≤ 0.435, P < 0.05), except for VPA (P = 0.440). This was also observed in age (<65/≥65yrs), COPD grades (GOLD 1-2/3-4) and in male patients (0.363 ≤ ρ ≤ 0.518, P < 0.05 except for VPA). No significant correlations were found in female patients (P > 0.05). Agreement was fair to moderate (0.36 ≤ κ ≤ 0.43; 73.6% ≤ %agreement ≤ 74.5%; 0.50 ≤ sensitivity ≤ 0.52; 0.84 ≤ specificity ≤ 0.91, 0.55 ≤ PPV ≤ 0.79, 0.72 ≤ NPV ≤ 0.82). CONCLUSION: The BPAAT may be useful to screen patients' PA, independently of age and COPD grade, and identify male patients who are insufficiently active. Care should be taken when using this tool to assess vigorous PA or female patients.

Environmental Awareness for Patients with COPD Undergoing Pulmonary Rehabilitation: Is It of Added Value?

Chronic obstructive pulmonary disease (COPD) is impacted by exposure to environmental contaminants. Improving health literacy on this topic might help to optimize health outcomes. We aimed to design and deliver a health-education session about the impact of environmental contaminants on respiratory symptoms and explore participants' perceptions on such session. Patients with COPD were recruited from a pulmonary rehabilitation (PR) program. Two focus groups were first conducted to explore knowledge amongst the group. Then, the session was designed and delivered, and three focus groups were conducted to obtain feedback from participants. Data were analyzed thematically by two independent researchers. Thirty-one patients (71 ± 8 years old, FEV1 = 47.6 ± 16.8% predicted; 74.2% male) were included. Prior to the session, participants recognized the importance of this topic and described avoidance strategies to deal with symptom triggering due to air pollution. After the session, participants had their knowledge validated, kept some avoidance strategies, but also adapted some "unavoidable" activities of daily living. Patients with COPD value education on this topic, and PR offers a friendly environment to discuss prevention and management strategies. Contents of the session are provided to help deliver these sessions. Future studies could investigate the effectiveness of this intervention on self-management and exacerbations of COPD.

Minimal Clinically Important Differences for Patient-Reported Outcome Measures of Fatigue in Patients With COPD Following Pulmonary Rehabilitation.

BACKGROUND: Fatigue is a burdensome and prevailing symptom in patients with COPD. Pulmonary rehabilitation (PR) improves fatigue; however, interpreting when such improvement is clinically relevant is challenging. Minimal clinically important differences (MCIDs) for instruments assessing fatigue are warranted to better tailor PR and guide clinical decisions. RESEARCH QUESTION: This study estimated MCIDs for the Functional Assessment of Chronic Illness Therapy-Fatigue Subscale (FACIT-FS), the modified FACIT-FS, and the Checklist Individual Strength-Fatigue Subscale in patients with COPD following PR. STUDY DESIGN AND METHODS: Data from patients with COPD who completed a 12-week community-based PR program were used to compute the MCIDs. The pooled MCID was estimated by calculating the arithmetic weighted mean, resulting from the combination of anchor-based (weight, two-thirds) and distribution-based (weight, one-third) methods. Anchors were patients' and physiotherapists' Global Rating of Change Scale, COPD Assessment Test, St. George's Respiratory Questionnaire (SGRQ), and exacerbations. To estimate MCIDs, we used mean change, receiver-operating characteristic curves, and linear regression analysis for anchor-based approaches, and 0.5 × SD, SE of measurement, 1.96 × SE of measurement, and minimal detectable change for distribution-based approaches. RESULTS: Fifty-three patients with COPD (79% male, 68.4 ± 7.6 years of age, and FEV1 48.7 ± 17.4% predicted) were included in the analysis. Exacerbations and the SGRQ-impact and the SGRQ-total scores fulfilled the requirements to be used as anchors. Pooled MCIDs were 4.7 for FACIT-FS, 3.8 for the modified FACIT-FS, and 9.3 for the Checklist Individual Strength-Fatigue Subscale. INTRPRETATION: The MCIDs proposed in this study can be used by different stakeholders to interpret PR effectiveness. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03799666; URL: www.clinicaltrials.gov.

Minimal Clinically Important Differences for Patient-Reported Outcome Measures of Cough and Sputum in Patients with COPD.

Background: Cough and sputum are highly prevalent in patients with chronic obstructive pulmonary disease (COPD). Pulmonary rehabilitation (PR) has shown to be effective in managing these symptoms. However, the interpretation of the magnitude of PR effects is hindered by the lack of minimal clinically important differences (MCIDs). Purpose: This study established MCIDs for the Leicester cough questionnaire (LCQ) and the cough and sputum assessment questionnaire (CASA-Q), in patients with COPD after PR. Patients and Methods: An observational prospective study was conducted in patients with COPD who participated in a 12-weeks community-based PR program. Anchor- (mean change, receiver operating characteristic curves and linear regression analysis) and distribution-based methods [0.5*standard deviation; standard error of measurement (SEM); 1.96*SEM; minimal detectable change and effect size] were used to compute the MCIDs. The anchors used were: i) patients and physiotherapists global rating of change scale, ii) COPD assessment test, iii) St. George's respiratory questionnaire and iv) occurrence of an exacerbation during PR. Pooled MCIDs were computed using the arithmetic weighted mean (2/3 for anchor- and 1/3 for distribution-based methods). Results: Forty-nine patients with COPD (81.6% male, 69.8±7.4years, FEV150.4±19.4%predicted) were used in the analysis. The pooled MCIDs were 1.3 for LCQ and for CASA-Q domains were: 10.6 - cough symptoms; 10.1 - cough impact; 9.5 - sputum symptoms and 7.8 - sputum impact. Conclusion: The MCIDs found in this study are potential estimates to interpret PR effects on cough and sputum, and may contribute to guide interventions.

Educational interventions to improve inhaler techniques and their impact on asthma and COPD control: a pilot effectiveness-implementation trial / Educação para a melhora da técnica inalatória e seu impacto no controle da asma e DPOC: um estudo piloto de efetividade-intervenção

ABSTRACT To assess the impact that educational interventions to improve inhaler techniques have on the clinical and functional control of asthma and COPD, we evaluated 44 participants before and after such an intervention. There was a significant decrease in the number of errors, and 20 patients (46%) significantly improved their technique regarding prior exhalation and breath hold. In the asthma group, there were significant improvements in the mean FEV1, FVC, and PEF (of 6.4%, 8.6%, and 8.3% respectively). Those improvements were accompanied by improvements in Control of Allergic Rhinitis and Asthma Test scores but not in Asthma Control Test scores. In the COPD group, there were no significant variations. In asthma patients, educational interventions appear to improve inhaler technique, clinical control, and functional control.

RESUMO Para avaliar o impacto do ensino da técnica inalatória no controle clínico e funcional de pacientes com asma ou DPOC, incluíram-se 44 participantes antes e após essa intervenção. Houve uma diminuição significativa no número de erros cometidos, sendo que 20 pacientes (46%) melhoraram significativamente sua técnica na expiração prévia e apneia final. No grupo asma, houve significativa melhora nas médias de FEV1 (6,4%), CVF (8,6%) e PFE (8,3%), e essa melhora correlacionou-se com os resultados no Control of Allergic Rhinitis and Asthma Test, mas não com os do Asthma Control Test. No grupo DPOC, não houve variações significativas. O ensino da técnica inalatória parece melhorar seu desempenho e os controles clínico e funcional em pacientes com asma.

Educational interventions to improve inhaler techniques and their impact on asthma and COPD control: a pilot effectiveness-implementation trial.

To assess the impact that educational interventions to improve inhaler techniques have on the clinical and functional control of asthma and COPD, we evaluated 44 participants before and after such an intervention. There was a significant decrease in the number of errors, and 20 patients (46%) significantly improved their technique regarding prior exhalation and breath hold. In the asthma group, there were significant improvements in the mean FEV1, FVC, and PEF (of 6.4%, 8.6%, and 8.3% respectively). Those improvements were accompanied by improvements in Control of Allergic Rhinitis and Asthma Test scores but not in Asthma Control Test scores. In the COPD group, there were no significant variations. In asthma patients, educational interventions appear to improve inhaler technique, clinical control, and functional control. RESUMO Para avaliar o impacto do ensino da técnica inalatória no controle clínico e funcional de pacientes com asma ou DPOC, incluíram-se 44 participantes antes e após essa intervenção. Houve uma diminuição significativa no número de erros cometidos, sendo que 20 pacientes (46%) melhoraram significativamente sua técnica na expiração prévia e apneia final. No grupo asma, houve significativa melhora nas médias de FEV1 (6,4%), CVF (8,6%) e PFE (8,3%), e essa melhora correlacionou-se com os resultados no Control of Allergic Rhinitis and Asthma Test, mas não com os do Asthma Control Test. No grupo DPOC, não houve variações significativas. O ensino da técnica inalatória parece melhorar seu desempenho e os controles clínico e funcional em pacientes com asma.

Predialysis hypernatremia is a prognostic marker in acute kidney injury in need of renal replacement therapy.

BACKGROUND AND OBJECTIVES: The present study aimed to evaluate the prognostic impact of predialysis dysnatremia in patients with acute kidney injury requiring renal replacement therapy (RRT). DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: A secondary analysis of a prospective multicenter cohort study was performed. Serum sodium (Na) concentrations were categorized immediately before the first RRT as normonatremia (135≤Na ≤145mEq/L), hyponatremia (mild [130≤Na ≤134mEq/L] or severe [Na ≤129mEq/L]), and hypernatremia (mild [146≤Na ≤155mEq/L] or severe [Na ≥156mEq/L]). Multivariable logistic regression was used to estimate the impact of sodium levels categories on hospital mortality. RESULTS: Dysnatremia occurred in 47.3% of 772 included patients. Hypernatremia was more frequent than hyponatremia (33.7% vs 13.6%, P=.001). Intensive care unit (ICU) and hospital mortality rates were 64.6% and 69%, respectively. Hospital mortality was higher in severe hypernatremia (89.1% [95% confidence interval {CI}, 78.7%-95.8%] vs 64.6% [CI, 59.8%-69.2%], P<.001, in normonatremia). Older patients, clinical admission, number of comorbidities, length of ICU stay before the beginning of RRT, and the number of organ dysfunctions were associated with higher hospital mortality. In multivariate analysis, severe hypernatremia (odds ratio, 2.87; 95% CI, 1.2-6.9), poor chronic heath status, severity of illness, sepsis, and lactate were independently associated with outcome. CONCLUSION: Almost 50% of patients with acute kidney injury in need of RRT in the ICU had mild or severe dysnatremia before dialysis initiation. Hypernatremia was the main sodium disturbance and independently associated with poor outcome in the study population.

Assessment of Inhalation Technique in Clinical and Functional Control of Asthma and Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Chronic obstructive pulmonary disease and asthma affect almost 300 million individuals. Inhaled therapy is often associated with technical errors reducing efficacy and compliance. OBJECTIVE: To evaluate the inhalation technique and its relation with clinical and functional control in asthma and chronic obstructive pulmonary disease. MATERIAL AND METHODS: Analytical cross-sectional study including patients with asthma and chronic obstructive pulmonary disease treated with any type of inhaler device. Demographic data and inquiry about previous teaching of inhalation technique were collected in all participants. Inhalation technique was evaluated in: Step 1 - device activation; Step 2 - previous expiration; Step 3 - inspiration; Step 4 - end inspiratory pause. Clinical control was assessed from the questionnaires Asthma Control Test, Control of Allergic Rhinitis and Asthma Test, modified Medical Research Council and Chronic Obstructive Pulmonary Disease Assessment Test. Spirometric evaluation was performed in all participants. RESULTS: From a total of 62 subjects, 74.19% made at least one error, mainly during step 2 (53.2%). Previous education on inhalation technique was associated with lower number of errors (p = 0.014). There was no association between number of errors and age (p = 0.321), years of diagnosis (p = 0.119) or spirometric evaluation (p > 0.05). In asthma an association was found between number of errors and Asthma Control Test (p = 0.032) and Control of Allergic Rhinitis and Asthma Test (p = 0.008). DISCUSSION AND CONCLUSION: Teaching inhalation technique has a positive impact on its future performance. Most patients make mistakes, affecting clinical control in asthma, although in chronic obstructive pulmonary disease no relation was found. This is an ongoing work that aims to reevaluate inhalation technique after patients' education and its further impact.

Introdução: A doença pulmonar obstrutiva crónica e a asma afectam quase 300 milhões de indivíduos em todo o mundo. A terapêutica inalatória associa-se frequentemente a erros na técnica realizada reduzindo a eficácia e adesão.Objectivo: Avaliar a técnica inalatória e sua relação com o controlo clínico e funcional em asma e doença pulmonar obstrutiva crónica. Material e Métodos: Estudo transversal analítico incluindo doentes com asma e doença pulmonar obstrutiva crónica medicados com dispositivos inalatórios. Recolheram-se dados demográficos e existência de ensino prévio da técnica. Avaliou-se a técnica inalatória em: Passo 1 - expiração prévia; Passo 2 - activação do dispositivo; Passo 3 - inspiração; Passo 4 - apneia final. O controlo clínico avaliou-se com os questionários Asthma Control Test, Control of Allergic Rhinitis and Asthma Test, modified Medical Research Council e Chronic Obstructive Pulmonary Disease Assessment Test. Todos os participantes realizaram avaliação espirométrica. Resultados: Obtiveram-se 62 participantes, dos quais 74,19% cometeram pelo menos um erro na inalação, principalmente na expiração prévia (53,2%). A existência prévia de ensino da técnica associou-se a menor n'º de erros (p = 0,014). Não houve associação entre n'º de erros e idade (p = 0,321), n'º de anos de diagnóstico (p = 0,119) ou avaliação espirométrica (p > 0,05). Na asma encontrou-se associação entre menor número de erros e Asthma Control Test (p = 0,032) e Control of Allergic Rhinitis and Asthma Test (p = 0,008). Discussão e Conclusão: O ensino da técnica inalatória melhora o seu desempenho futuro. A maioria dos doentes comete erros afectando o controlo clínico na asma, apesar de na doença pulmonar obstrutiva crónica não se verificar nenhuma associação. Este trabalho encontra-se a decorrer procurando reavaliar os doentes após o ensino da técnica e verificar o seu impacto subsequente.

The evaluation of sequential platelet counts has prognostic value for acute kidney injury patients requiring dialysis in the intensive care setting.

OBJECTIVE: To evaluate the prognostic value of platelet counts in acute kidney injury patients requiring renal replacement therapy. METHODS: This prospective cohort study was performed in three tertiary-care hospitals. Platelet counts were obtained upon admission to the intensive care unit and during the first week of renal replacement therapy on days 1, 3, 5 and 7. The outcome of interest was the hospital mortality rate. With the aim of minimizing individual variation, we analyzed the relative platelet counts on days 3, 5, 7 and at the point of the largest variation during the first week of renal replacement therapy. Logistic regression analysis was used to test the prognostic value of the platelet counts. RESULTS: The study included 274 patients. The hospital mortality rate was 62%. The survivors had significantly higher platelet counts upon admission to the intensive care unit compared to the non-survivors [175.5×10(3)/mm(3) (108.5-259×10(3)/mm(3)) vs. 148×10(3)/mm(3) (80-141×10(3)/mm(3))] and during the first week of renal replacement therapy. The relative platelet count reductions were significantly associated with a higher hospital mortality rate compared with the platelet count increases (70% vs. 44% at the nadir, respectively). A relative platelet count reduction >60% was significantly associated with a worse outcome (mortality rate=82.6%). Relative platelet count variations and the percentage of reduction were independent risk factors of hospital mortality during the first week of renal replacement therapy. CONCLUSION: Platelet counts upon admission to the intensive care unit and at the beginning of renal replacement therapy as well as sequential platelet count evaluation have prognostic value in acute kidney injury patients requiring renal replacement therapy.

The evaluation of sequential platelet counts has prognostic value for acute kidney injury patients requiring dialysis in the intensive care setting

OBJECTIVE: To evaluate the prognostic value of platelet counts in acute kidney injury patients requiring renal replacement therapy. METHODS: This prospective cohort study was performed in three tertiary-care hospitals. Platelet counts were obtained upon admission to the intensive care unit and during the first week of renal replacement therapy on days 1, 3, 5 and 7. The outcome of interest was the hospital mortality rate. With the aim of minimizing individual variation, we analyzed the relative platelet counts on days 3, 5, 7 and at the point of the largest variation during the first week of renal replacement therapy. Logistic regression analysis was used to test the prognostic value of the platelet counts. RESULTS: The study included 274 patients. The hospital mortality rate was 62%. The survivors had significantly higher platelet counts upon admission to the intensive care unit compared to the non-survivors [175.5×103/mm3 (108.5-259×103/mm3) vs. 148×103/mm3 (80−141×103/mm3)] and during the first week of renal replacement therapy. The relative platelet count reductions were significantly associated with a higher hospital mortality rate compared with the platelet count increases (70% vs. 44% at the nadir, respectively). A relative platelet count reduction >60% was significantly associated with a worse outcome (mortality rate = 82.6%). Relative platelet count variations and the percentage of reduction were independent risk factors of hospital mortality during the first week of renal replacement therapy. CONCLUSION: Platelet counts upon admission to the intensive care unit and at the beginning of renal replacement therapy as well as sequential platelet count evaluation have prognostic value in acute kidney injury patients requiring renal replacement therapy. .

Regression of albuminuria and hypertension and arrest of severe renal injury by a losartan-hydrochlorothiazide association in a model of very advanced nephropathy.

Treatments that effectively prevent chronic kidney disease (CKD) when initiated early often yield disappointing results when started at more advanced phases. We examined the long-term evolution of renal injury in the 5/6 nephrectomy model (Nx) and the effect of an association between an AT-1 receptor blocker, losartan (L), and hydrochlorothiazide (H), shown previously to be effective when started one month after Nx. Adult male Munich-Wistar rats underwent Nx, being divided into four groups: Nx+V, no treatment; Nx+L, receiving L monotherapy; Nx+LH, receiving the L+H association (LH), and Nx+AHHz, treated with the calcium channel blocker, amlodipine, the vascular relaxant, hydralazine, and H. This latter group served to assess the effect of lowering blood pressure (BP). Rats undergoing sham nephrectomy (S) were also studied. In a first protocol, treatments were initiated 60 days after Nx, when CKD is at a relatively early stage. In a second protocol, treatments were started 120 days after Nx, when glomerulosclerosis and interstitial fibrosis are already advanced. In both protocols, L treatment promoted only partial renoprotection, whereas LH brought BP, albuminuria, tubulointerstitial cell proliferation and plasma aldosterone below pretreatment levels, and completely detained progression of renal injury. Despite normalizing BP, the AHHz association failed to prevent renal damage, indicating that the renoprotective effect of LH was not due to a systemic hemodynamic action. These findings are inconsistent with the contention that thiazides are innocuous in advanced CKD. In Nx, LH promotes effective renoprotection even at advanced stages by mechanisms that may involve anti-inflammatory and intrarenal hemodynamic effects, but seem not to require BP normalization.

Outcomes of cancer and non-cancer patients with acute kidney injury and need of renal replacement therapy admitted to general intensive care units.

BACKGROUND: Studies on cancer patients with acute kidney injury (AKI) are restricted to specialized intensive care units (ICUs). The aim of this study was to compare the characteristics and outcomes of cancer and non-cancer patients requiring renal replacement therapy (RRT) for AKI in general ICUs. METHODS: A prospective cohort study was conducted in 14 ICUs from three tertiary care hospitals. A total of 773 (non-cancer 85%; cancer 15%) consecutive patients were included over a 44-month period. Logistic regression was used to identify factors associated with hospital mortality. RESULTS: Continuous RRT was used in 79% patients. The main contributing factors for AKI were sepsis (72%) and ischaemia/shock (66%); AKI was multifactorial in 87% of cancer and in 71% non-cancer patients. Hospital mortality rates were higher in cancer (78%) than in non-cancer patients (68%) (P=0.042). However, in multivariate analyses, older age, medical admission, poor chronic health status, comorbidities, ICU days until the RRT start and number of associated organ dysfunctions were associated with hospital mortality. The diagnosis of cancer was not independently associated with mortality [odds ratio=1.54 (95% confidence interval, 0.88-2.62), P=0.115]. Mortality in cancer patients was mostly dependent on the number of associated organ dysfunctions. Of note, 85% cancer patients recovered renal function at hospital discharge. CONCLUSIONS: In general ICUs, one in six patients requiring RRT has cancer. Despite a relatively higher mortality, the presence of cancer was not independently associated with mortality in the present cohort.