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BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a remarkable kidney tropism. While kidney effects are common in severe coronavirus disease 2019 (COVID-19), data on non-severe courses are limited. Here we provide a multilevel analysis of kidney outcomes after non-severe COVID-19 to test for eventual kidney sequela. METHODS: This cross-sectional study investigates individuals after COVID-19 and matched controls recruited from the Hamburg City Health Study (HCHS) and its COVID-19 program. The HCHS is a prospective population-based cohort study within the city of Hamburg, Germany. During the COVID-19 pandemic the study additionally recruited subjects after polymerase chain reaction-confirmed SARS-CoV-2 infections. Matching was performed by age, sex and education. Main outcomes were estimated glomerular filtration rate (eGFR), albuminuria, Dickkopf3, haematuria and pyuria. RESULTS: A total of 443 subjects in a median of 9 months after non-severe COVID-19 were compared with 1328 non-COVID-19 subjects. The mean eGFR was mildly lower in post-COVID-19 than non-COVID-19 subjects, even after adjusting for known risk factors {ß = -1.84 [95% confidence interval (CI) -3.16 to -0.52]}. However, chronic kidney disease [odds ratio (OR) 0.90 (95% CI 0.48-1.66)] or severely increased albuminuria [OR 0.76 (95% CI 0.49-1.09)] equally occurred in post-COVID-19 and non-COVID-19 subjects. Haematuria, pyuria and proteinuria were also similar between the two cohorts, suggesting no ongoing kidney injury after non-severe COVID-19. Further, Dickkopf3 was not increased in the post-COVID-19 cohort, indicating no systematic risk for ongoing GFR decline [ß = -72.19 (95% CI -130.0 to -14.4)]. CONCLUSION: While mean eGFR was slightly lower in subjects after non-severe COVID-19, there was no evidence for ongoing or progressive kidney sequela.
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COVID-19 , Piuria , Humanos , COVID-19/complicaciones , COVID-19/epidemiología , SARS-CoV-2 , Albuminuria , Estudios de Cohortes , Estudios Prospectivos , Pandemias , Hematuria , Estudios Transversales , Riñón , Progresión de la EnfermedadRESUMEN
OBJECTIVE: There is a paucity of current figures on the prevalence of carotid and lower extremity peripheral arterial disease (PAD) and abdominal aortic aneurysm (AAA) as well as the associated cardiovascular risk factors to support considerations on screening programmes. METHODS: In the population based Hamburg City Health Study, participants between 45 and 74 years were randomly recruited. In the current cross sectional analysis of the first 10 000 participants enrolled between February 2016 and November 2018, the prevalence of carotid artery disease (intima-media thickness ≥ 1 mm), lower extremity PAD (ankle brachial index ≤ 0.9), and AAA (aortic diameter ≥ 30 mm) was determined. Multivariable logistic regression models were applied to determine the association between vascular diseases and risk factors. To account for missing values, multiple imputation was performed. RESULTS: A total of 10 000 participants were analysed (51.1% females, median age 63 years, median body mass index 26.1 kg/m2). In medians, the intima media thickness was 0.74 mm (interquartile range [IQR] 0.65 - 0.84), the ankle brachial index 1.04 (IQR 0.95 - 1.13), and the aortic diameter 17.8 mm (IQR 16.1 - 19.6). Concerning risk factors, 64% self reported any smoking, 39% hypertension, 5% coronary artery disease, 3% congestive heart failure, 5% atrial fibrillation, and 3% history of stroke or myocardial infarction, respectively. In males, the prevalence of carotid artery disease, lower extremity PAD, and AAA were 35.3%, 22.7%, and 1.3%, respectively, and in females, 23.4%, 24.8%, and 0.2%, respectively. Higher age and current smoking were likewise associated with higher prevalence while the impact of variables varied widely. CONCLUSION: In this large population based cohort study of 10 000 subjects from Hamburg, Germany, a strikingly high prevalence of PAD was revealed. Almost 45% suffered from any index disease, while AAA was only diagnosed in 1.3% of males and 0.2% of females. The high prevalence of atherosclerotic disease and associated cardiovascular risk factors underline that it is essential to increase awareness and fuel efforts for secondary prevention.
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AIMS: Long-term sequelae may occur after SARS-CoV-2 infection. We comprehensively assessed organ-specific functions in individuals after mild to moderate SARS-CoV-2 infection compared with controls from the general population. METHODS AND RESULTS: Four hundred and forty-three mainly non-hospitalized individuals were examined in median 9.6 months after the first positive SARS-CoV-2 test and matched for age, sex, and education with 1328 controls from a population-based German cohort. We assessed pulmonary, cardiac, vascular, renal, and neurological status, as well as patient-related outcomes. Bodyplethysmography documented mildly lower total lung volume (regression coefficient -3.24, adjusted P = 0.014) and higher specific airway resistance (regression coefficient 8.11, adjusted P = 0.001) after SARS-CoV-2 infection. Cardiac assessment revealed slightly lower measures of left (regression coefficient for left ventricular ejection fraction on transthoracic echocardiography -0.93, adjusted P = 0.015) and right ventricular function and higher concentrations of cardiac biomarkers (factor 1.14 for high-sensitivity troponin, 1.41 for N-terminal pro-B-type natriuretic peptide, adjusted P ≤ 0.01) in post-SARS-CoV-2 patients compared with matched controls, but no significant differences in cardiac magnetic resonance imaging findings. Sonographically non-compressible femoral veins, suggesting deep vein thrombosis, were substantially more frequent after SARS-CoV-2 infection (odds ratio 2.68, adjusted P < 0.001). Glomerular filtration rate (regression coefficient -2.35, adjusted P = 0.019) was lower in post-SARS-CoV-2 cases. Relative brain volume, prevalence of cerebral microbleeds, and infarct residuals were similar, while the mean cortical thickness was higher in post-SARS-CoV-2 cases. Cognitive function was not impaired. Similarly, patient-related outcomes did not differ. CONCLUSION: Subjects who apparently recovered from mild to moderate SARS-CoV-2 infection show signs of subclinical multi-organ affection related to pulmonary, cardiac, thrombotic, and renal function without signs of structural brain damage, neurocognitive, or quality-of-life impairment. Respective screening may guide further patient management.
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COVID-19 , COVID-19/diagnóstico , COVID-19/epidemiología , Estudios de Cohortes , Humanos , SARS-CoV-2 , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
OBJECTIVE: Nephrogenic systemic fibrosis (NSF) is a progressive fibrosing disorder that may develop in patients with chronic kidney disease after administration of gadolinium (Gd)-based contrast agents (GBCAs). In the setting of impaired renal clearance of GBCAs, Gd deposits in various tissues and fibrosis subsequently develops. However, the precise mechanism by which fibrosis occurs in NSF is incompletely understood. Because other profibrotic agents, such as silica or asbestos, activate the nucleotide-binding oligomerisation domain (NOD)-like receptor protein 3 (NLRP3) inflammasome and initiate interleukin (IL)-1ß release with the subsequent development of fibrosis, we evaluated the effects of GBCAs on inflammasome activation. METHODS: Bone marrow derived macrophages from C57BL/6, Nlrp3(-/-) and Asc(-/-) mice were incubated with three Gd-containing compounds and IL-1ß activation and secretion was detected by ELISA and western blot analysis. Inflammasome activation and regulation was investigated in IL-4- and interferon (IFN)γ-polarised macrophages by ELISA, quantitative real time (qRT)-PCR and NanoString nCounter analysis. Furthermore, C57BL/6 and Nlrp3(-/-)mice were intraperitoneally injected with GBCA and recruitment of inflammatory cells to the peritoneum was analysed by fluorescence-activated cell sorting (FACS). RESULTS: Free Gd and GBCAs activate the NLRP3 inflammasome and induce IL-1ß secretion in vitro. Gd-diethylenetriaminepentaacetic acid also induces the recruitment of neutrophils and inflammatory monocytes to the peritoneum in vivo. Gd activated IL-4-polarised macrophages more effectively than IFNγ-polarised macrophages, which preferentially expressed genes known to downregulate inflammasome activity. CONCLUSIONS: These data suggest that Gd released from GBCAs triggers a NLRP3 inflammasome-dependent inflammatory response that leads to fibrosis in an appropriate clinical setting. The preferential activation of IL-4-differentiated macrophages is consistent with the predominantly fibrotic presentation of NSF.
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Proteínas Portadoras/efectos de los fármacos , Medios de Contraste/farmacología , Gadolinio/farmacología , Inflamasomas/efectos de los fármacos , Interleucina-1beta/efectos de los fármacos , Macrófagos/efectos de los fármacos , Dermopatía Fibrosante Nefrogénica/inmunología , Peritoneo/efectos de los fármacos , Peritonitis/inmunología , Animales , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/inmunología , Proteínas Adaptadoras de Señalización CARD , Proteínas Portadoras/genética , Proteínas Portadoras/inmunología , Medios de Contraste/efectos adversos , Modelos Animales de Enfermedad , Gadolinio/efectos adversos , Gadolinio DTPA/efectos adversos , Gadolinio DTPA/farmacología , Inflamasomas/inmunología , Interleucina-1beta/inmunología , Interleucina-1beta/metabolismo , Macrófagos/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteína con Dominio Pirina 3 de la Familia NLR , Dermopatía Fibrosante Nefrogénica/inducido químicamente , Dermopatía Fibrosante Nefrogénica/genética , Compuestos Organometálicos/efectos adversos , Compuestos Organometálicos/farmacología , Peritoneo/inmunología , Peritonitis/inducido químicamente , Peritonitis/genéticaAsunto(s)
Trasplante de Riñón , Nefritis Intersticial/microbiología , Complicaciones Posoperatorias/microbiología , Tuberculosis/complicaciones , Aloinjertos/patología , Antituberculosos/administración & dosificación , Humanos , Riñón/patología , Masculino , Persona de Mediana Edad , Nefritis Intersticial/patología , Complicaciones Posoperatorias/patología , Tuberculosis/tratamiento farmacológicoRESUMEN
Fas, a TNF family receptor, is activated by the membrane protein Fas ligand expressed on various immune cells. Fas signaling triggers apoptosis and induces inflammatory cytokine production. Among the Fas-induced cytokines, the IL-1ß family cytokines require proteolysis to gain biological activity. Inflammasomes, which respond to pathogens and danger signals, cleave IL-1ß cytokines via caspase-1. However, the mechanisms by which Fas regulates IL-1ß activation remain unresolved. In this article, we demonstrate that macrophages exposed to TLR ligands upregulate Fas, which renders them responsive to receptor engagement by Fas ligand. Fas signaling activates caspase-8 in macrophages and dendritic cells, leading to the maturation of IL-1ß and IL-18 independently of inflammasomes or RIP3. Hence, Fas controls a novel noncanonical IL-1ß activation pathway in myeloid cells, which could play an essential role in inflammatory processes, tumor surveillance, and control of infectious diseases.
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Caspasa 8/fisiología , Interleucina-18/biosíntesis , Interleucina-1beta/biosíntesis , Proteína Serina-Treonina Quinasas de Interacción con Receptores/fisiología , Receptor fas/fisiología , Animales , Caspasa 8/genética , Caspasa 8/metabolismo , Células Dendríticas/enzimología , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Activación Enzimática/inmunología , Proteína de Dominio de Muerte Asociada a Fas/deficiencia , Proteína de Dominio de Muerte Asociada a Fas/genética , Proteína de Dominio de Muerte Asociada a Fas/fisiología , Inflamasomas/metabolismo , Inflamasomas/fisiología , Macrófagos Peritoneales/enzimología , Macrófagos Peritoneales/inmunología , Macrófagos Peritoneales/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Proteína Serina-Treonina Quinasas de Interacción con Receptores/deficiencia , Proteína Serina-Treonina Quinasas de Interacción con Receptores/genética , Transducción de Señal/genética , Transducción de Señal/inmunologíaRESUMEN
INTRODUCTION: Kidney dysfunction (KD) is a risk factor for cerebrovascular events and has been shown to have a detrimental effect on outcome after stroke. We evaluated the influence of KD at admission and pre-existing diagnosis of chronic kidney disease (CKD) before thrombectomy for anterior circulation stroke on functional independence and mortality 90 days after stroke in this cross-sectional study. PATIENTS AND METHODS: We included patients with acute ischemic stroke in the anterior circulation treated with thrombectomy at our hospital between June 2015 and May 2022. We analyzed clinical characteristics, laboratory values and pre-existing diagnosis of CKD. KD at admission was defined as glomerular filtration rate (GFR) <60 ml/min/1.73 m2. Outcomes were defined as a modified Rankin Scale Score of 0-2 for functional independence and mortality at 90 days. We fitted multivariate regression analysis to examine the influence of pre-treatment KD and pre-diagnosed CKD on outcome. RESULTS: Nine hundred fifty-three patients were included in this analysis (mean age 73.8 years, 54.2% female). KD was present in 31.8%, and patients with KD were older and more often female, presented more often with comorbidities such as arterial hypertension, diabetes, and atrial fibrillation, and were less often independent before the index stroke. In multivariate analysis adjusted for age, independence before the index stroke, diabetes, hypertension, atrial fibrillation, initial NIHSS, thrombolysis treatment, and recanalization outcome, KD on admission had no significant influence on functional independence 90 days after stroke, but predicted mortality with an odds ratio of 1.80 (95% CI 1.23-2.63, p = 0.003). This influence also persisted when controlling for pre-diagnosed CKD (OR 1.60, 95% CI 1.05-2.43, p = 0.027). DISCUSSION: KD might function as a surrogate parameter for comorbidity burden and thus increased risk of mortality in this cohort. CONCLUSIONS: KD on admission is associated with an 80% higher risk of mortality at 90 days after stroke thrombectomy independent of cardiovascular risk factors and CKD awareness. KD on admission should not exclude patients from thrombectomy but might support prognostic evaluation.
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Insuficiencia Renal Crónica , Trombectomía , Humanos , Femenino , Masculino , Anciano , Insuficiencia Renal Crónica/mortalidad , Insuficiencia Renal Crónica/complicaciones , Estudios Transversales , Anciano de 80 o más Años , Persona de Mediana Edad , Factores de Riesgo , Tasa de Filtración Glomerular , Accidente Cerebrovascular Isquémico/mortalidad , Accidente Cerebrovascular Isquémico/complicaciones , Accidente Cerebrovascular/mortalidad , Factores de Riesgo de Enfermedad CardiacaRESUMEN
BACKGROUND: The increasing admissions of very elderly patients to intensive care units (ICUs) over recent decades highlight a growing need for understanding acute kidney injury (AKI) in this population. Although these individuals are potentially at high risk for AKI and adverse outcomes, data on AKI in this population is scarce. This study investigates the AKI incidence and outcomes of critically-ill patients aging at least 90 years. METHODS: This retrospective cohort study conducted at the Department of Intensive Care Medicine, University Medical Centre Hamburg-Eppendorf, Germany (2008-2020), investigates AKI incidence and outcomes between 2008 and 2020 in critically-ill patients aged ≥ 90 years. AKI was defined according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria using creatinine dynamics and/or urine output. Primary endpoint was overall mortality after 1 year. Secondary endpoints were in-hospital mortality, length of ICU and hospital stay. RESULTS: During the study period 92,958 critically-ill patients were treated and 1108 were ≥ 90 years. Of these, 1054 patients had available creatinine values and were included in the present study. AKI occurred in 24.4%, mostly classified as mild (17.5%). AKI was independently associated with a significant increase in overall mortality (HR 1.21, 95 %-CI: 1.01-1.46), in-hospital mortality (OR 2, 1.41-2.85), length of ICU (+2.8 days, 2.3-3.3) and hospital stay (+2.3 days, 0.9-3.7). Severity escalated these effects, but even mild AKI showed significance. Introducing urine-based criteria increased incidence but compromised mortality prediction. CONCLUSIONS: AKI is a frequent complication in very elderly critically-ill patients. Occurrence of AKI at any stage was associated with increased mortality. Predictive ability applied to AKI defined by creatinine but not urine output. Careful attention of creatinine dynamics is essential in very elderly ICU-patients.
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BACKGROUND: Various sequelae have been described after nonsevere coronavirus disease 2019 (COVID-19), but knowledge on postacute effects on blood pressure is limited. METHODS: This is a cross-sectional analysis of blood pressure profiles in individuals after nonsevere COVID-19 compared with matched population-based individuals without prior COVID-19. Data were derived from the ongoing and prospective Hamburg City Health Study, a population-based study in Hamburg, Germany, and its associated COVID-19 program, which included individuals at least 4âmonths after COVID-19. Matching was performed by age, sex, education, and preexisting hypertension in a 1â:â4 ratio. RESULTS: Four hundred and thirty-two individuals after COVID-19 (mean age 56.1âyears) were matched to 1728 controls without prior COVID-19 (56.2âyears). About 92.8% of COVID-19 courses were mild or moderate, only 7.2% were hospitalized, and no individual had been treated on an intensive care unit. Even after adjustment for relevant competing risk factors, DBP [+4.7âmmHg, 95% confidence interval (95% CI) 3.97-5.7, P â<â0.001] was significantly higher in individuals after COVID-19. For SBP, a trend towards increased values was observed (+1.4âmmHg, 95% CI -0.4 to 3.2, P â=â0.120). Hypertensive blood pressures at least 130/80âmmHg (according to the ACC/AHA guideline) and at least 140/90âmmHg (ESC/ESH guideline) occurred significantly more often in individuals after COVID-19 than matched controls (odds ratio 2.0, 95% CI 1.5-2.7, P â<â0.001 and odds ratio 1.6, 95% CI 1.3-2.0, P â<â0.001, respectively), mainly driven by changes in DBP. CONCLUSION: Blood pressure is higher in individuals after nonsevere COVID-19 compared with uninfected individuals suggesting a significant hypertensive sequela.
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COVID-19 , Hipertensión , Humanos , Persona de Mediana Edad , Presión Sanguínea/fisiología , Estudios Transversales , Estudios Prospectivos , COVID-19/complicacionesRESUMEN
BACKGROUND: Critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requiring veno-venous extracorporeal membrane oxygenation (vv-ECMO) are at risk for acute kidney injury (AKI). Currently, the incidence of AKI and progression to kidney replacement therapy (RRT) in critically ill patients with vv-ECMO for severe COVID-19 and implications on outcome are still unclear. METHODS: Retrospective analysis at the University Medical Center Hamburg-Eppendorf (Germany) between March 1st, 2020 and July 31st, 2021. Demographics, clinical parameters, AKI, type of organ support, length of ICU stay, mortality and severity scores were assessed. RESULTS: Ninety-one critically ill patients with SARS-CoV-2 requiring ECMO were included. The median age of the study population was 57 (IQR 49-64) years and 67% (n = 61) were male. The median SAPS II and SOFA Score on admission were 40 (34-46) and 12 (10-14) points, respectively. We observed that 45% (n = 41) developed early-AKI, 38% (n = 35) late-AKI and 16% (n = 15) no AKI during the ICU stay. Overall, 70% (n = 64) of patients required RRT during the ICU stay, 93% with early-AKI and 74% with late-AKI. Risk factors for early-AKI were younger age (OR 0.94, 95% CI 0.90-0.99, p = 0.02) and SAPS II (OR 1.12, 95% CI 1.06-1.19, p < 0.001). Patients with and without RRT were comparable regarding baseline characteristics. SAPS II (41 vs. 37 points, p < 0.05) and SOFA score (13 vs. 12 points, p < 0.05) on admission were significantly higher in patients receiving RRT. The median duration of ICU (36 vs. 28 days, p = 0.27) stay was longer in patients with RRT. An ICU mortality rate in patients with RRT in 69% (n = 44) and in patients without RRT of 56% (n = 27) was observed (p = 0.23). CONCLUSION: Critically ill patients with severe SARS-CoV-2 related ARDS requiring vv-ECMO are at high risk of early acute kidney injury. Early-AKI is associated with age and severity of illness, and presents with high need for RRT. Mortality in patients with RRT was comparable to patients without RRT.
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BACKGROUND: Acute kidney injury (AKI) after transcatheter aortic valve implantation (TAVI) is a serious complication which is associated with increased mortality. The RenalGuard system was developed to reduce the risk of AKI after contrast media exposition by furosemide-induced diuresis with matched isotonic intravenous hydration. The aim of this study was to examine the effect of the RenalGuard system on the occurrence of AKI after TAVI in patients with chronic kidney disease. METHODS: The present study is a single-center randomized trial including patients with severe aortic valve stenosis undergoing TAVI. Overall, a total of 100 patients treated by TAVI between January 2017 and August 2018 were randomly assigned to a periprocedural treatment with the RenalGuard system or standard treatment by pre- and postprocedural intravenous hydration. Primary endpoint was the occurrence of AKI after TAVI, and secondary endpoints were assessed according to valve academic research consortium 2 criteria. RESULTS: Overall, the prevalence of AKI was 18.4% (n = 18). The majority of these patients developed mild AKI according to stage 1. Comparing RenalGuard to standard therapy, no significant differences were observed in the occurrence of AKI (RenalGuard: 21.3%; control group: 15.7%; p = 0.651). In addition, there were no differences between the groups with regard to 30-day and 12-month mortality and procedure-associated complication rates. CONCLUSION: In this randomized trial, we did not detect a reduction in AKI after TAVI by using the RenalGuard system. A substantial number of patients with chronic kidney disease developed AKI after TAVI, whereas the majority presented with mild AKI according to stage 1 (ClinicalTrials.gov number NCT04537325).
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Background: Collateral effects and consequences of the coronavirus disease 19 (COVID-19) pandemic on kidney transplant recipients remain widely unknown. Methods: This retrospective cohort study examined changes in admission rates, incidences of diseases leading to hospitalization, in-patient procedures, and maintenance medication in long-term kidney transplant recipients with functioning graft during the early COVID-19 pandemic in Germany. Data were derived from a nationwide health insurance database. Analysis was performed from March 15 to September 30 and compared the years 2019 and 2020. Effects on mortality and adverse allograft events were compared with COVID-19-attributed effects. Results: A total of 7725 patients were included in the final analysis. Admissions declined in 2020 by 17%, with the main dip during a 3-month lockdown (-31%) but without a subsequent rebound. Incidences for hospitalization did not increase for any investigated disease entities, whereas decreasing trends were noted for non-COVID-19 pulmonary and urogenital infections (incidence rate ratio 0.8, 95% CI, 0.62 to 1.03, and 0.82, 95% CI, 0.65 to 1.04, respectively). Non-COVID-19 hospital stays were 0.6 days shorter (P=0.03) and not complicated by increased dialysis, ventilation, or intensive care treatment rates. In-hospital and 90-day mortality remained stable. Incidences of severe COVID-19 requiring hospitalization was 0.09 per 1000 patient-days, and in-hospital mortality was 9%. A third (31%) of patients with calcineurin-inhibitor medication and without being hospitalized for COVID-19 reduced doses by at least 25%, which was associated with an increased allograft rejection risk (adjusted hazard ratio 1.29, 95% CI, 1.02 to 1.63). COVID-19 caused 17% of all deaths but had no significant association with allograft rejections. All-cause mortality remained stable (incidence rate ratio 1.15, 95% CI, 0.91 to 1.46), also when restricting analysis to patients with no or outpatient-treated COVID-19 (0.97, 95% CI, 0.76 to 1.25). Conclusion: Despite significant collateral effects, mortality remained unchanged during the early COVID-19 pandemic. Considerable temporary reductions in admissions are safe, whereas reducing immunosuppression results in increased allograft rejection risk.
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COVID-19 , Trasplante de Riñón , Control de Enfermedades Transmisibles , Humanos , Trasplante de Riñón/efectos adversos , Pandemias , Diálisis Renal , Estudios RetrospectivosRESUMEN
Background: Coronavirus disease 2019 (COVID-19) has resulted in high hospitalization rates worldwide. Acute kidney injury (AKI) in patients hospitalized for COVID-19 is frequent and associated with disease severity and poor outcome. The aim of this study was to investigate the incidence of kidney replacement therapy (KRT) in critically ill patients with COVID-19 and its implication on outcome. Methods: We retrospectively analyzed all COVID-19 patients admitted to the Department of Intensive Care Medicine at the University Medical Center Hamburg-Eppendorf (Germany) between 1 March 2020 and 31 July 2021. Demographics, clinical parameters, type of organ support, length of intensive care unit (ICU) stay, mortality and severity scores were assessed. Results: Three-hundred critically ill patients with COVID-19 were included. The median age of the study population was 61 (IQR 51-71) years and 66% (n = 198) were male. 73% (n = 219) of patients required invasive mechanical ventilation. Overall, 68% (n = 204) of patients suffered from acute respiratory distress syndrome and 30% (n = 91) required extracorporeal membrane oxygenation (ECMO). We found that 46% (n = 139) of patients required KRT. Septic shock (OR 11.818, 95% CI: 5.941-23.506, p < 0.001), higher simplified acute physiology scores (SAPS II) (OR 1.048, 95% CI: 1.014-1.084, p = 0.006) and vasopressor therapy (OR 5.475, 95% CI: 1.127-26.589, p = 0.035) were independently associated with the initiation of KRT. 61% (n = 85) of patients with and 18% (n = 29) without KRT died in the ICU (p < 0.001). Cox regression found that KRT was independently associated with mortality (HR 2.075, 95% CI: 1.342-3.208, p = 0.001) after adjusting for confounders. Conclusion: Critically ill patients with COVID-19 are at high risk of acute kidney injury with about half of patients requiring KRT. The initiation of KRT was associated with high mortality.
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OBJECTIVE: The current study aimed to determine the relationship between chronic kidney disease (CKD) and major 12-month outcomes for patients with in-hospital treatment for symptomatic peripheral arterial occlusive disease (PAOD). METHODS: An analysis of the prospective longitudinal multicentric cohort study with 12-month follow-up was conducted including patients who underwent endovascular or open surgery for symptomatic PAOD at 35 German vascular centres (initial study protocol: NCT03098290). Severity of CKD was grouped into four stages combining information about the estimated glomerular filtration rate (eGFR) at baseline and dialysis dependency. Outcomes included overall mortality as well as the two composite endpoints of amputation or death, and of major cardiovascular events (MACE). 12-month incidences and adjusted hazard ratios were estimated using the Kaplan-Meier function and Cox proportional hazard models. RESULTS: A total of 4354 patients (32% female, 69 years mean age, 68% intermittent claudication, 69% percutaneous endovascular revascularisation) were included and followed for 244 days in median. Thereof, 22% had any CKD and 5% had end stage kidney disease (ESKD) at baseline. The 12-month overall mortality rate was 3.6% (95% CI 2.3-4.9) with 96 events in the entire cohort: 147 were amputated or died (5.3%, 95% CI 5.2-5.3), and 277 had a MACE (9.5%, 95% CI 9.4-9.5). When compared with patients without kidney disease, ESKD was significantly associated with overall mortality (HR 1.9; 95% CI 1.1-3.5), amputation or death (HR 2.4; 95% CI 1.4-4.1), and MACE (HR 2.0; 95% CI 1.3-3.2). CONCLUSIONS: In the current study on mid-term outcomes after invasive revascularisation for symptomatic PAOD, one out of five patients suffered from any CKD while those few with ESKD had twice the odds of death, of amputation or death, and of major adverse cardiovascular events after twelve months. These results emphasise that concomitant CKD and its impact on outcomes should be considered by severity while mild and moderate grades should not lead to ineffectual treatment strategies.
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INTRODUCTION: Seven of 10 patients with non-dialysis chronic kidney disease (CKD) experience burdensome persistent somatic symptoms (PSS). Despite the high prevalence and relevance for quality of life, disease progression and mortality, the pathogenesis of PSS in CKD remains poorly understood. The SOMA.CK study aims to investigate biopsychosocial predictors and their interactions for PSS in non-dialysis CKD and to develop a multivariate prognostic prediction model for PSS in CKD. METHODS AND ANALYSIS: The study is a mixed-methods cohort study with assessments at baseline, 6 and 12 months. It aims to include 330 patients with CKD stages G2-4 (eGFR=15-89 mL/min/1.73 m2). Primary outcome is the CKD-specific somatic symptom burden assessed with the CKD Symptom Burden Index. Secondary outcomes include quality of life, general somatic symptom burden and functioning. The interplay of biomedical (eg, biomarkers, epigenetics), treatment-related (eg, therapies and medication) and psychosocial variables (eg, negative affectivity, expectations) will be investigated to develop a prognostic prediction model for PSS. In an embedded mixed-methods approach, an experimental study in 100 patients using an affective picture paradigm will test the effect of negative affect induction on symptom perception. An embedded longitudinal qualitative study in 40-50 newly diagnosed patients will use thematic analysis to explore mechanisms of symptom development after receiving a CKD diagnosis. SOMA.CK is part of the interdisciplinary research unit 'Persistent SOMAtic Symptoms ACROSS Diseases'. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of the Hamburg Medical Association (2020-10195-BO-ff). Findings will be disseminated through peer-reviewed publications, scientific conferences, the involvement of our patient advisory board and the lay public. Focusing on subjective symptom burden instead of objective disease markers will fundamentally broaden the understanding of PSS in CKD and pave the path for the development of mechanism-based tailored interventions. TRIAL REGISTRATION NUMBER: ISRCTN16137374.
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Síntomas sin Explicación Médica , Insuficiencia Renal Crónica , Humanos , Estudios de Cohortes , Calidad de Vida/psicología , Insuficiencia Renal Crónica/complicaciones , Investigación CualitativaRESUMEN
Extrapulmonary manifestations of COVID-19 have gained attention due to their links to clinical outcomes and their potential long-term sequelae1. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) displays tropism towards several organs, including the heart and kidney. Whether it also directly affects the liver has been debated2,3. Here we provide clinical, histopathological, molecular and bioinformatic evidence for the hepatic tropism of SARS-CoV-2. We find that liver injury, indicated by a high frequency of abnormal liver function tests, is a common clinical feature of COVID-19 in two independent cohorts of patients with COVID-19 requiring hospitalization. Using autopsy samples obtained from a third patient cohort, we provide multiple levels of evidence for SARS-CoV-2 liver tropism, including viral RNA detection in 69% of autopsy liver specimens, and successful isolation of infectious SARS-CoV-2 from liver tissue postmortem. Furthermore, we identify transcription-, proteomic- and transcription factor-based activity profiles in hepatic autopsy samples, revealing similarities to the signatures associated with multiple other viral infections of the human liver. Together, we provide a comprehensive multimodal analysis of SARS-CoV-2 liver tropism, which increases our understanding of the molecular consequences of severe COVID-19 and could be useful for the identification of organ-specific pharmacological targets.