RESUMO
Liver failure in the intensive care unit (ICU), whether acute or acute-on-chronic, remains a serious condition with reduced functions, various metabolite and toxin accumulation in the systemic circulation, and a high mortality rate. While transplantation remains the treatment of choice, the lack of organ transplants necessitates finding alternative solutions. Within the last years, several therapies aiming to support liver function have been developed in order to serve as a bridge to liver transplantation or as replacement therapy, allowing regeneration of the injured liver. In those therapies, nonbiological extracorporeal liver support devices are the most widely used, mainly based on detoxification by eliminating accumulated toxins notably by adsorption on specific membranes and/or with plasmapheresis. One of the most recent techniques is the double plasma molecular adsorption system combining plasma filtration and two specific adsorption membranes, which is largely described and studied in this chapter. This technique seems promising to remove deleterious toxins, cytokines and bilirubin in particular, is fairly simple to use, does not require a specific machine (it works on continuous renal replacement therapy machines), and has given encouraging results in the pilot studies published recently, in association with plasmapheresis or alone. However, further studies and evaluations are needed before this technique can be used routinely in ICU.
Assuntos
Fígado , Toxinas Biológicas , Humanos , Adsorção , Plasmaferese , Circulação Extracorpórea , PlasmaRESUMO
Abstract We conducted a retrospective cohort study to report the clinical characteristics, incidence and out-comes of patients with severe COVID-19 with acute kidney injury (AKI). One-hundred and sixtytwo intensive care unit (ICU) admitted patients in a tertiary level hospital in the city of Buenos Aires with COVID-19 diagnosis were included. We hypothesized that COVID-19 related AKI would develop in the period of more severe hypoxemia as an early event and late AKI would be more probably related to intensive care unit complications. For this purpose, we divided subjects into two groups: those with early AKI and late AKI, before and after day 14 from symptom onset, respectively. A stepwise multivariate analysis was conducted to find possible AKI predictors. AKI incidence was 43.2% (n = 70) of the total patients admitted into ICU with severe COVID-19, 11.1% (n = 18) required renal replacement therapy. In-hospital mortality was higher (58.6%) for the AKI group. AKI occurred on a median time of 10 (IQR 5.5-17.5) days from symptom onset. A history of hypertension or heart failure, age and invasive mechanical ventilation (IMV) requirement were identified as risk factors. Late AKI (n = 25, 35.7%) was associated with sepsis and nephrotoxic exposure, whereas early AKI occurred closer to the timing of IMV initiation and was more likely to have an unknown origin. In conclusion, AKI is frequent among critically ill patients with severe COVID-19 and it is associated with higher in-hospital mortality.
Resumen Llevamos a cabo un estudio retrospectivo con el objetivo de describir las características clínicas, incidencia y desenlaces de los pacientes con injuria renal aguda (IRA) asociada a la COVID-19. Se incluyeron 162 pacientes con diagnóstico de COVID-19 admitidos en una unidad de cuidados intensivos en un hospital de tercer nivel en la Ciudad de Buenos Aires. Nuestra hipótesis consistió en que la IRA asociada a COVID-19 sería un evento temprano asociado a la gravedad de la hipoxemia y la IRA tardía se relacionaría con complicaciones propias de la UCI. Por ello se clasificó la IRA en temprana y tardía, según sucediera antes o después de los 14 días desde el inicio de síntomas. Se realizó un análisis multivariado mediante regresión logística escalonada para evaluar posibles factores de riesgo. La incidencia de IRA fue de 43.2% (n = 70), 11.1% (n = 18) requirieron terapia de reemplazo renal. La mortalidad intrahospitalaria fue mayor (58.6%) en el grupo con IRA. El diagnóstico de IRA se realizó en una mediana de 10 (IQR = 5.5-17.5) días desde el inicio de los síntomas. El antecedente de hipertensión e insuficiencia cardíaca, la edad y el requerimiento de ventilación mecánica invasiva (VMI) fueron identificados como factores de riesgo para IRA. La IRA tardía (n = 25, 35.7%) estuvo asociada a sepsis y expo sición a nefrotóxicos, mientras que la IRA temprana (n = 45, 64.2%) estuvo temporalmente asociada al inicio de la VMI y en muchos casos no se pudo filiar una etiología. En conclusión, la IRA es una complicación frecuente en pacientes con COVID-19 grave y está asociada a una alta mortalidad intrahospitalaria.
RESUMO
We conducted a retrospective cohort study to report the clinical characteristics, incidence and outcomes of patients with severe COVID-19 with acute kidney injury (AKI). One-hundred and sixtytwo intensive care unit (ICU) admitted patients in a tertiary level hospital in the city of Buenos Aires with COVID-19 diagnosis were included. We hypothesized that COVID-19 related AKI would develop in the period of more severe hypoxemia as an early event and late AKI would be more probably related to intensive care unit complications. For this purpose, we divided subjects into two groups: those with early AKI and late AKI, before and after day 14 from symptom onset, respectively. A stepwise multivariate analysis was conducted to find possible AKI predictors. AKI incidence was 43.2% (n = 70) of the total patients admitted into ICU with severe COVID-19, 11.1% (n = 18) required renal replacement therapy. In-hospital mortality was higher (58.6%) for the AKI group. AKI occurred on a median time of 10 (IQR 5.5-17.5) days from symptom onset. A history of hypertension or heart failure, age and invasive mechanical ventilation (IMV) requirement were identified as risk factors. Late AKI (n = 25, 35.7%) was associated with sepsis and nephrotoxic exposure, whereas early AKI occurred closer to the timing of IMV initiation and was more likely to have an unknown origin. In conclusion, AKI is frequent among critically ill patients with severe COVID-19 and it is associated with higher in-hospital mortality.
Llevamos a cabo un estudio retrospectivo con el objetivo de describir las características clínicas, incidencia y desenlaces de los pacientes con injuria renal aguda (IRA) asociada a la COVID-19. Se incluyeron 162 pacientes con diagnóstico de COVID-19 admitidos en una unidad de cuidados intensivos en un hospital de tercer nivel en la Ciudad de Buenos Aires. Nuestra hipótesis consistió en que la IRA asociada a COVID-19 sería un evento temprano asociado a la gravedad de la hipoxemia y la IRA tardía se relacionaría con complicaciones propias de la UCI. Por ello se clasificó la IRA en temprana y tardía, según sucediera antes o después de los 14 días desde el inicio de síntomas. Se realizó un análisis multivariado mediante regresión logística escalonada para evaluar posibles factores de riesgo. La incidencia de IRA fue de 43.2% (n = 70), 11.1% (n = 18) requirieron terapia de reemplazo renal. La mortalidad intrahospitalaria fue mayor (58.6%) en el grupo con IRA. El diagnóstico de IRA se realizó en una mediana de 10 (IQR = 5.5-17.5) días desde el inicio de los síntomas. El antecedente de hipertensión e insuficiencia cardíaca, la edad y el requerimiento de ventilación mecánica invasiva (VMI) fueron identificados como factores de riesgo para IRA. La IRA tardía (n = 25, 35.7%) estuvo asociada a sepsis y exposición a nefrotóxicos, mientras que la IRA temprana (n = 45, 64.2%) estuvo temporalmente asociada al inicio de la VMI y en muchos casos no se pudo filiar una etiología. En conclusión, la IRA es una complicación frecuente en pacientes con COVID-19 grave y está asociada a una alta mortalidad intrahospitalaria.
Assuntos
Injúria Renal Aguda , COVID-19 , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Adulto , COVID-19/complicações , Teste para COVID-19 , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Terapia de Substituição Renal/efeitos adversos , Estudos Retrospectivos , Fatores de RiscoRESUMO
Introducción: El desarrollo de disfunción renal en el contexto de una falla cardíaca aguda se conoce como síndrome cardiorrenal (SCR) tipo 1. El empeoramiento de la función renal (EFR) durante la internación es un predictor de mal pronóstico. La cistatina C ha surgido como un marcador de función renal alternativo a la creatinina. Objetivo: Demostrar la utilidad clínica de la cistatina C como predictor de EFR y factor pronóstico en pacientes con insuficiencia cardíaca aguda y sin disfunción renal evaluada por creatinina al ingreso. Material y métodos: Se llevó a cabo un estudio observacional, prospectivo, de pacientes consecutivos con diagnóstico de insuficiencia cardíaca aguda y sin disfunción renal, definida como un valor de creatinina < 1,3 mg/dl al ingreso. Se realizó un dosaje de cistatina C al ingreso. El punto final primario fue EFR y los secundarios fueron mortalidad hospitalaria, mortalidad total y reinternación por insuficiencia cardíaca. Resultados: Se incluyeron 166 pacientes con una mediana de edad de 85 años (IIC 77,7-89). La incidencia de EFR fue del 29,7%, con una mortalidad hospitalaria del 3,1% y una mortalidad total del 24,4%. La mediana de seguimiento fue de 193 días. El valor de cistatina C fue significativamente mayor en los pacientes que desarrollaron EFR (1,72 ± 0,58 mg/dl vs. 1,51 ± 0,41 mg/dl; p = 0,03) y en los pacientes que murieron en el seguimiento (1,76 ± 0,49 mg/dl vs. 1,51 ± 0,46 mg/dl; p = 0,004). La cistatina C resultó un predictor independiente de mortalidad (OR 3,03, IC 95% 1,22-7,47) y de EFR (OR 2,38, IC 95% 1,02-5,5) en el análisis multivariado. Se halló un punto de corte óptimo de 1,6 mg/dl de cistatina, con una sensibilidad del 61,22% y una especificidad del 60,34% para el desarrollo de EFR y del 61,54% y 61,98%, respectivamente, para mortalidad total. Conclusión: El valor de cistatina C al ingreso es predictor de desarrollo de EFR durante la internación y de mayor mortalidad en esta población con insuficiencia cardíaca aguda y función renal conservada al ingreso.
RESUMO
The MDRD equation to estimate glomerular filtration rate (GFR) is the most widely used strategy to assess chronic kidney disease. Nonetheless, for the individual patient the true GFR can be underestimated with the risk of diagnosing a more elevated CKD stage. This novel CKD-EPI equation would improve accuracy and precision of estimations, and several authors recommend this new equation replace the former. In our country there is only a limited registration of these comparisons performed on a large number of patients. Therefore, our aim was to develop a comparison in a wide cohort of patients. The concordance between both equations to assign the GFR stages was determined by using the MDRD formula as a reference. The mean difference of GFR obtained with both equations as well as the Bland-Altman analysis were calculated. A cohort of 9319 individuals, of whom 67% were females, aged 58 ± 20 years, with serum creatinine values of 1.6 ± 1.03 mg/dl, was studied. In the whole group, CKD-EPI displayed an average GFR 0.61 ml/min/1.73 m2 larger than MDRD (p: NS). For CKD stages 2 and 3A the mean estimated GFR difference was 6.95 ± 4.76 and 3.21 ± 3.31, while the concordance was 81 and 74% respectively. The percentage of patients with GFR < 60 ml/min/1.73 m2, decreased from 76.3% with the former equation to 70.1% with the latter. The novel equation CKD-EPI reduces the number of patients with GFR values lower than 60 ml/min/1.73 m2 and consequently assigns a higher GFR stage to a considerable quantity of individuals.
Assuntos
Creatinina/sangue , Taxa de Filtração Glomerular/fisiologia , Nefropatias/fisiopatologia , Doença Crônica , Estudos de Coortes , Feminino , Humanos , Nefropatias/sangue , Nefropatias/diagnóstico , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Índice de Gravidade de DoençaRESUMO
La ecuación MDRD para la estimación del índice de filtrado glomerular (IFG), es la estrategia más utilizada para evaluar pacientes con enfermedad renal crónica (ERC). Sin embargo, puede subestimar el IFG con el riesgo de asignar al paciente a estadios más avanzados de ERC. La nueva ecuación CKD-EPI, mejoraría la exactitud y precisión de las estimaciones. Sus autores sugieren que reemplace a la anterior. No habiendo comparaciones de estas ecuaciones aplicadas en un gran número de pacientes en nuestro país, nuestro objetivo fue realizarla en una amplia cohorte de pacientes. Se evaluó la concordancia de asignación en estadios de ERC entre ambas ecuaciones, tomando como referencia los datos surgidos de MDRD. Se calculó la media de las diferencias de los IFG obtenidos empleando ambas ecuaciones y se aplicó el análisis estadístico de Bland-Altman. Se estudió una cohorte de 9 319 pacientes con una media de creatinina sérica de 1.60 ± 1.03 mg/dl, 67% de sexo femenino y edad media 58 ± 20 años. En el grupo total, CKD-EPI presentó una media de IFG 0.61 ml/min/1.73 m² mayor que MDRD (p: NS). En los estadios 2 y 3A las medias del IFG fueron respectivamente 6.95 ± 4.76 y 3.21 ± 3.31, y la concordancia de 81 y 74%. El porcentaje de pacientes con un IFG menor de 60 ml/min/1.73 m², se redujo de 76.3% (MDRD) a 70.1% (CKD-EPI). Por lo tanto, la nueva ecuación CKD-EPI disminuye el número de pacientes con IFG debajo de 60 ml/min/1.73 m² y asigna estadios de IFG más elevado a un número mayor de pacientes.
The MDRD equation to estimate glomerular filtration rate (GFR) is the most widely used strategy to assess chronic kidney disease. Nonetheless, for the individual patient the true GFR can be underestimated with the risk of diagnosing a more elevated CKD stage. This novel CKD-EPI equation would improve accuracy and precision of estimations, and several authors recommend this new equation replace the former. In our country there is only a limited registration of these comparisons performed on a large number of patients. Therefore, our aim was to develop a comparison in a wide cohort of patients. The concordance between both equations to assign the GFR stages was determined by using the MDRD formula as a reference. The mean difference of GFR obtained with both equations as well as the Bland-Altman analysis were calculated. A cohort of 9 319 individuals, of whom 67% were females, aged 58 ± 20 years, with serum creatinine values of 1.6 ± 1.03 mg/dl, was studied. In the whole group, CKD-EPI displayed an average GFR 0.61 ml/min/1.73 m² larger than MDRD (p: NS). For CKD stages 2 and 3A the mean estimated GFR difference was 6.95 ± 4.76 and 3.21 ± 3.31, while the concordance was 81 and 74% respectively. The percentage of patients with GFR < 60 ml/min/1.73 m², decreased from 76.3% with the former equation to 70.1% with the latter. The novel equation CKD-EPI reduces the number of patients with GFR values lower than 60 ml/min/1.73 m² and consequently assigns a higher GFR stage to a considerable quantity of individuals.
Assuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Creatinina/sangue , Taxa de Filtração Glomerular/fisiologia , Nefropatias/fisiopatologia , Doença Crônica , Estudos de Coortes , Nefropatias/sangue , Nefropatias/diagnóstico , Valor Preditivo dos Testes , Índice de Gravidade de DoençaRESUMO
Pamidronate (APD), a third-generation bisphosphonate, has proven to be useful in haemodialysis (HD) patients with ectopic calcifications and hypercalcaemia. Little is known about bisphosphonates clearance in patients undergoing HD. The authors' main objective was to study HD removal and clearance of APD. In total, 23 HD-requiring anuric end-stage renal disease (ESRD) adult individuals (12 men) aged 61.7 +/- 13 (mean +/- SD) years were admitted into the study. APD clearance and elimination were evaluated by (99m)Technetium APD (half-life 6 h). In total, 1 mg of labelled APD was injected via the arteriovenous graft prior to the start of HD. Blood samples were then drawn from the arterial (predialyser) and venous (postdialyser) lines of the extracorporeal circuit 2 h after the HD onset. In a subgroup of patients (n: 15) the dialysate was collected and quantified during the three initial HD hours. Venous APD concentrations (postdialyser) were 72 + 7% of arterial (predialyser) concentrations. Mean APD clearance was 69.3 + 16.6 mL/min, and mean APD extraction during dialysis session was 31.6 + 10.1%. In the present study involving HD-requiring anuric ESRD patients APD was successfully eliminated by HD. At the dose administered here none of the participants reported adverse events. APD is a potentially useful drug to be administered to HD-requiring ESRD patients, the understanding of its removal during HD as well as its dialytic clearance allows for a safer management of a drug that is usually eliminated by renal excretion.
Assuntos
Difosfonatos/metabolismo , Difosfonatos/farmacocinética , Diálise Renal , Difosfonatos/química , Humanos , Masculino , Pessoa de Meia-Idade , PamidronatoRESUMO
BACKGROUND: Hyperhomocysteinaemia is an independent risk factor for cardiovascular disease with a remarkable prevalence in patients with chronic renal failure (CRF). Low doses of folic acid (FA) with or without vitamin B6 and B12 has been shown to effectively reduce plasma homocysteine (Hcy). The aim of this study was to compare the short-term effects of two different oral doses of FA (5 vs 15 mg/d) on plasma Hcy levels in subjects suffering from moderate-severe CRF. METHODS: A double-blind, double-dummy, comparative, two-stage randomised study was performed. Seventeen patients aged 45-71 years, with glomerular filtration rates between 15.4-50 mL/min 1.73/m2 were randomly assigned to receive FA 5 mg/d (FA-5, n: 8) or FA 15 mg/d (FA-15, n: 9) for 30 days. At the end of this 30-day double-blind period, all the participants were placed on FA 5 mg/d (open period), for 5 additional months. Both groups were also supplemented with vitamins B1, B6 and B12 throughout the trial. Blood samples were drawn at 0, 15, 30, 90 and 180 days to assess Hcy, complete blood count (CBC) and sequential multichannel analysis (SMA). Chest X-ray and a 12-lead electrocardiogram (ECG) were also performed. RESULTS: Plasma Hcy (mean +/- SEM) decreased from 27.9 +/- 1.4 (baseline) to 15.1 +/- 0.6, 13.3 +/- 0.9, 14.1 +/- 0.5 and 13.8 +/- 0.5 micromol/L (FA-5) and from 28.8 +/- 2.7 to 15.6 +/- 1.2, 14.4 +/- 1.3, 13.0 +/- 0.7 and 13.1 +/- 0.6 micromol/L (FA-15) at days 15, 30, 90 and 180, respectively. (P < 0.01 from day 15 to 180 vs baseline for both groups with no differences between them). Renal function remained stable throughout the entire period of the study in all but one patient in whom it deteriorated to pre-end stage disease. No adverse cardiovascular events developed during the trial. CONCLUSION: Both folic acid doses induced a significant and similar decrease in plasma Hcy in subjects with moderate-severe chronic renal failure. The possible dose-related effect of this approach in reducing the risk of accelerated sclerotic vascular disease and cardiovascular events in this especially vulnerable population should be a matter of further investigation.