RESUMO
Introduction: There have been few studies investigating acute kidney injury (AKI) in patients with yellow fever (YF). The objective of this study was to identify the risk factors for AKI and death in such patients. Methods: We evaluated 95 consecutive critically ill adult patients with the sylvatic form of YF, as confirmed by reverse-transcriptase polymerase chain reaction, in Brazil. The outcome measures were AKI (as defined by Kidney Disease: Improving Global Outcomes [KDIGO] criteria) and in-hospital death. Results: Of the 95 patients, 73 (76.8%) had AKI and 59 (62.1%) died from it. A total of 70 patients (73.7%) required dialysis because of AKI. After adjusting for age, sex, and the Simplified Acute Physiology Score 3 (SAPS 3), we found that elevated fractional excretion of sodium and requiring dialysis were independent risk factors for in-hospital mortality and that proteinuria correlated with AKI-associated mortality. Conclusion: Our findings indicate that, in patients with sylvatic YF, AKI is common and is associated with significant mortality. The data presented here could prove useful for improving understanding of the pathogenesis of AKI in YF and informing decisions regarding the care of the affected patients.
RESUMO
Background: The incidence of acute kidney injury (AKI) is high in intensive care units (ICUs), and a better understanding of AKI is needed. Early chronic kidney disease is associated with urinary concentration inability and AKI recovery with increased urinary solutes in humans. Whether the inability of the kidneys to concentrate urine and excrete solutes at appropriate levels could occur prior to the diagnosis of AKI is still uncertain, and the associated mechanisms have not been studied. Methods: In this single-center prospective observational study, high AKI risk in ICU patients was followed up for 7 days or until ICU discharge. They were grouped as "AKI" or "No AKI" according to their AKI status throughout admission. We collected daily urine samples to measure solute concentrations and osmolality. Data were analyzed 1 day before AKI, or from the first to the fifth day of admission in the "No AKI" group. We used logistic regression models to evaluate the influence of the variables on future AKI diagnosis. The expression of kidney transporters in urine was evaluated by Western blotting. Results: We identified 29 patients as "No AKI" and 23 patients as "AKI," the latter being mostly low severity AKI. Urinary sodium excretion was lower in "AKI" patients prior to AKI diagnosis, particularly in septic patients. The expression of Na+/H+ exchanger (NHE3), a urinary sodium transporter, was higher in "AKI" patients. Conclusions: Urinary sodium excretion is low before an AKI episode in ICU patients, and high expressions of proximal tubule sodium transporters might contribute to this.
RESUMO
BACKGROUND: Coronavirus disease 2019 (COVID-19) may predispose patients to thrombotic events. The best anticoagulation strategy for continuous renal replacement therapy (CRRT) in such patients is still under debate. The purpose of this study was to evaluate the impact that different anticoagulation protocols have on filter clotting risk. METHODS: This was a retrospective observational study comparing two different anticoagulation strategies (citrate only and citrate plus intravenous infusion of unfractionated heparin) in patients with acute kidney injury (AKI), associated or not with COVID-19 (COV + AKI and COV - AKI, respectively), who were submitted to CRRT. Filter clotting risks were compared among groups. RESULTS: Between January 2019 and July 2020, 238 patients were evaluated: 188 in the COV + AKI group and 50 in the COV - AKI group. Filter clotting during the first filter use occurred in 111 patients (46.6%). Heparin use conferred protection against filter clotting (HR = 0.37, 95% CI 0.25-0.55), resulting in longer filter survival. Bleeding events and the need for blood transfusion were similar between the citrate only and citrate plus unfractionated heparin strategies. In-hospital mortality was higher among the COV + AKI patients than among the COV - AKI patients, although it was similar between the COV + AKI patients who received heparin and those who did not. Filter clotting was more common in patients with D-dimer levels above the median (5990 ng/ml). In the multivariate analysis, heparin was associated with a lower risk of filter clotting (HR = 0.28, 95% CI 0.18-0.43), whereas an elevated D-dimer level and high hemoglobin were found to be risk factors for circuit clotting. A diagnosis of COVID-19 was marginally associated with an increased risk of circuit clotting (HR = 2.15, 95% CI 0.99-4.68). CONCLUSIONS: In COV + AKI patients, adding systemic heparin to standard regional citrate anticoagulation may prolong CRRT filter patency by reducing clotting risk with a low risk of complications.
Assuntos
Injúria Renal Aguda/tratamento farmacológico , Ácido Cítrico/farmacologia , Terapia de Substituição Renal Contínua/instrumentação , Heparina/farmacologia , Filtros Microporos/normas , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Adulto , COVID-19/complicações , COVID-19/epidemiologia , Ácido Cítrico/efeitos adversos , Ácido Cítrico/uso terapêutico , Estudos de Coortes , Terapia de Substituição Renal Contínua/métodos , Terapia de Substituição Renal Contínua/estatística & dados numéricos , Feminino , Heparina/efeitos adversos , Heparina/uso terapêutico , Humanos , Estimativa de Kaplan-Meier , Masculino , Filtros Microporos/estatística & dados numéricos , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
OBJECTIVES: The primary objective is to test if heparin added to a standard regional anticoagulation protocol based on citrate is able to reduce dialysis circuit losses by clotting without increasing the risk of thrombocytopenia or bleeding, in patients with COVID-19 with acute kidney injury requiring dialysis. TRIAL DESIGN: Randomized, parallel-group, open-label trial, with two arms (ratio 1:1) comparing different continuous renal replacement therapy anticoagulation strategies. PARTICIPANTS: Eligibility conditions: All ICU patients of University of Sao Paulo General Hospital (Hospital das Clínicas), Brazil will be screened for eligibility conditions. Adults (> 18 years old) with confirmed COVID-19 and acute kidney injury requiring dialysis with agreement between ICU and nephrology teams for the introduction of renal continuous replacement therapy in daily ICU rounds. Continuous renal replacement therapy will be prescribed by consulting nephrologists based on standard clinical guidelines, including acute kidney injury with hemodynamic instability plus hyperkalemia, severe acidosis, volume overload, respiratory distress, multiorgan failure or some combination of these factors. DATA COLLECTION: Patients demographics and associated clinical data and comorbidities will be recorded at ICU entry. Demographic information will include the patient's age, sex, and admission dates. Clinical data comprise comorbidities, APACHE 2, SAPS 3, need for mechanical ventilation, and use of vasopressor drugs. Physiological data collected by the day of CRRT start will be vital signs, the arterial oxygen tension/fraction of inspired oxygen (PaO2/FiO2) index, and serum creatinine, blood urea nitrogen, bilirubin, hemoglobin, hematocrit, platelets, white blood cell count levels and Peak D-dimer levels. Patients will be analyzed for the first 72h of CRRT, and they will be evaluated regarding clinical variables, filter patency and any adverse events that could be related to the anticoagulation choice, as bleeding (mild or major) or low platelets counts (<100.000 ui/uL) during treatment period. Mild and major bleeding will be defined by hemorrhagic event without clinical impact or hemoglobin (Hb) fall lesser than 1g/dL and hemorrhagic event with clinical impact or Hb fall higher than 1g/dL, respectively. EXCLUSION CRITERIA: Hypersensitivity to any of the substances going to be used in the study (Citric acid dextrosol 2.2% and unfractionated heparin); Previous diagnosis of coagulopathy or thrombophilia; Contraindication to the use of unfractionated heparin; Risk of citrate poisoning - (Lactate> 30 mg/dL, international normalized ratio > 2.5, Total bilirubin> 15 mg/dL); Pregnancy; Patients unlikely to survive for more than 24 hours. The trial is being undertaken at the University of Sao Paulo General Hospital (Hospital das Clinicas), Brazil. INTERVENTION AND COMPARATOR: Group A (control) - Patients on continuous renal replacement therapy (blood flow 150 ml/min, dose of 30 mL/Kg/h) receiving anticoagulation with sodium citrate at 4 mmol/L Group B (experiment): Patients on continuous hemodialysis (blood flow 150 mL/min, dose of 30 mL/Kg/h) receiving anticoagulation with sodium citrate at 4 mmol/L associated with unfractionated heparin at 10 U/Kg/h. MAIN OUTCOMES: The percentage of clotted dialyzers within 72 hours in each of the studied groups (Primary outcome) Secondary outcomes: Number of dialyzers used in the first 72 hours of dialysis protocol, Mortality in the first 72 h of dialysis protocol, Bleeding events (Major or minor) in the first 72 h of dialysis protocol, Thrombocytopenia (less than 50.000 platelets) proportion in the first 72 h of dialysis protocol, Dialysis efficiency (Urea sieving) - variation in urea sieving between the first, second and third days of dialysis protocol, Continuous renal replacement therapy pressures (Arterial, Venous, dialysate and pre-filter pressure) in the first 72 h of dialysis protocol, in-hospital mortality. RANDOMIZATION: RedCapâ randomization - 2 blocks randomization by D-dimer level (5000ng/dL cut-off) and catheter site (Right Internal Jugular versus other sites) with 1:1 allocation ratio. BLINDING (MASKING): No blinding - Open label format NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): Total number of patients 90 (45 per group) TRIAL STATUS: Trial version 2.0 - ongoing recruitment. First recruitment: June 29, 2020 Estimated date for last recruitment: December 31, 2020 TRIAL REGISTRATION: Responsible Party: University of Sao Paulo General Hospital (Hospital das Clinicas) ClinicalTrials.gov Identifier: NCT04487990 , registered July 27, 2020, ReBec www.ensaiosclinicos.gov.br/rg/RBR-45kf9p/ Other Study ID Numbers: U1111-1252-0194 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1) In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
Assuntos
Injúria Renal Aguda , Infecções por Coronavirus , Monitoramento de Medicamentos/métodos , Heparina , Pandemias , Pneumonia Viral , Diálise Renal , Trombose/prevenção & controle , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Adulto , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Coagulação Sanguínea/efeitos dos fármacos , COVID-19 , Infecções por Coronavirus/sangue , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Hemoglobinas/análise , Hemorragia/etiologia , Hemorragia/prevenção & controle , Heparina/administração & dosagem , Heparina/efeitos adversos , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Pneumonia Viral/sangue , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Diálise Renal/efeitos adversos , Diálise Renal/métodos , Risco Ajustado/métodos , Trombocitopenia/etiologia , Trombocitopenia/prevenção & controle , Trombose/complicaçõesRESUMO
BACKGROUND Corpus callosum agenesis (CCA) is one of the most common congenital brain abnormalities, and is associated with neurodevelopmental and neuropsychiatric disorders. In CCA, defects in osmoregulation have been reported. This report presents a rare case of chronic hyponatremia associated with the syndrome of inappropriate antidiuresis (SIAD) in a woman with CCA. CASE REPORT A 41-year-old woman presented to the renal unit with symptomatic hyponatremia. In her past medical history, she had a four-year history of systemic arterial hypertension and Sjögren's syndrome, and a three-year history of systemic lupus erythematosus (SLE), which was treated with cyclophosphamide. She had CCA but with irregular neurological follow-up. During the previous eight years, her plasma sodium levels ranged from between 118-134 mEq/L. On this hospital admission, she had plasma hypo-osmolality, measured in milli-osmoles per kilogram of H2O (mOsm/kg H2O), of 251 mOsm/Kg H2O, and a urinary hyper-osmolality of 545 mOsm/Kg H2O, and increased level of plasma antidiuretic hormone (ADH) (1.8 pg/ml). Bone densitometry was consistent with osteoporosis. The patient remained asymptomatic during her hospital stay. Chronic hyponatremia associated with the SIAD was diagnosed. Water restriction and increased protein intake resulted in a partial improvement in the serum sodium level (128-134 mEq/L). The patient was discharged from the hospital with outpatient follow-up. CONCLUSIONS A rare case of chronic hyponatremia due to the SIAD associated with CCA is reported that demonstrates the importance of correct diagnosis, management, and clinical follow-up of the SIAD, including bone densitometry.
Assuntos
Agenesia do Corpo Caloso/complicações , Hiponatremia/etiologia , Síndrome de Secreção Inadequada de HAD/complicações , Síndrome de Secreção Inadequada de HAD/terapia , Adulto , Agenesia do Corpo Caloso/diagnóstico por imagem , Análise Química do Sangue , Doença Crônica , Feminino , Seguimentos , Humanos , Hiponatremia/fisiopatologia , Hiponatremia/terapia , Síndrome de Secreção Inadequada de HAD/diagnóstico , Imageamento por Ressonância Magnética/métodos , Doenças Raras , Medição de Risco , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Some studies have suggested that early institution of renal replacement therapy (RRT) might be associated with improved outcomes in patients with acute renal failure (ARF). STUDY DESIGN: A systematic review and meta-analysis of randomized controlled trials and cohort comparative studies to assess the effect of early RRT on mortality in patients with ARF. SETTING & POPULATION: Hospitalized adult patients with ARF. SELECTION CRITERIA FOR STUDIES: We searched several databases for studies that compared the effect of "early" and "late" RRT initiation on mortality in patients with ARF. We included studies of various designs. INTERVENTION: Early RRT as defined in the individual studies. OUTCOMES: The primary outcome measure was the effect of early RRT on mortality stratified by study design. The pooled risk ratio (RR) for mortality was compiled using a random-effects model. Heterogeneity was evaluated by means of subgroup analysis and meta-regression. RESULTS: We identified 23 studies (5 randomized or quasi-randomized controlled trials, 1 prospective and 16 retrospective comparative cohort studies, and 1 single-arm study with a historic control group). By using meta-analysis of randomized trials, early RRT was associated with a nonsignificant 36% mortality risk reduction (RR, 0.64; 95% confidence interval, 0.40 to 1.05; P = 0.08). Conversely, in cohort studies, early RRT was associated with a statistically significant 28% mortality risk reduction (RR, 0.72; 95% confidence interval, 0.64 to 0.82; P < 0.001). The overall test for heterogeneity among cohort studies was significant (P = 0.005). Meta-regression yielded no significant associations; however, early dialysis therapy was associated more strongly with lower mortality in smaller studies (n < 100) by means of subgroup analysis. LIMITATIONS: Paucity of randomized controlled trials, use of variable definitions of early RRT, and publication bias preclude definitive conclusions. CONCLUSION: This hypothesis-generating meta-analysis suggests that early initiation of RRT in patients with ARF might be associated with improved survival, calling for an adequately powered randomized controlled trial to address this question.
Assuntos
Injúria Renal Aguda/terapia , Terapia de Substituição Renal/métodos , Injúria Renal Aguda/mortalidade , Saúde Global , Humanos , Taxa de Sobrevida , Fatores de TempoRESUMO
Hemodialysis (HD) and peritoneal dialysis are associated with inflammatory events and immunological incompetence. The purpose of this study was to evaluate the effect of both uremia and dialysis modality on the production of cytokines and reactive oxygen species (ROS) by monocytes. four groups of subjects were studied: 28 chronic kidney disease (CKD) patients, 14 chronic HD patients, 14 patients on continuous ambulatory peritoneal dialysis (CAPD) patients, and 14 healthy volunteers, peripheral blood mononuclear cells (PBMC) were isolated from blood samples and incubated for 24 hr with or without lipopolysaccharide (LPS). TNF-alpha and IL-10 production by PBMC and serum levels of these cytokines were quantified by ELISA. Aliquots of whole blood were incubated in vitro and ROS production and phagocytosis were quantified by flow cytometry. Compared to the control group, Staphylococcus aureus-stimulated ROS production by monocytes was significantly lower in the HD group. The highest levels of unstimulated TNF-alpha production in vitro were observed in the HD group. In the CKD group, as well as in the whole population, there were a negative correlation between TNF-alpha production by unstimulated PBMC and ROS production by S. aureus-stimulated monocytes and a positive correlation between PMA-stimulated ROS production by monocytes and unstimulated and LPS-stimulated IL-10 production by PBMC suggesting that the pro-inflammatory state in CKD patients is associated with decreased response to infectious challenges.