Fractional excretion of sodium and potassium and urinary strong ion difference in the evaluation of persistent AKI in sepsis.

OBJECTIVE: To evaluate the diagnostic performance of FENa (Fractional excretion of sodium), FEK (fractional excretion of potassium) and uSID (urinary strong ion difference) in predicting pAKI in sepsis and septic shock. DESIGN: Retrospective cohort study. SETTING: Two intensive care units in Argentina. PATIENTS: Adult patients with a confirmed diagnosis of sepsis or septic shock and AKI, and had a urinary biochemistry within 24h of the AKI diagnosis. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: We evaluated the diagnostic accuracy of FENa, FEK and uSID through a ROC (Receiver Operating Characteristic) curve analysis. RESULTS: 80 patients were included. 40 patients presented pAKI. pAKI group had higher APACHE, SOFA score, and mortality rate. In the ROC curve analysis, uSID had no diagnostic utility (AUC=0.52, p=0.69). FENa presented moderate accuracy showing an AUC of 0.71 (95% CI 0.60-0.83; p=0.001), while FEK presented low accuracy with an AUC of 0.69 (95% CI 0.57-0.80; p=0.04). The optimal Youden point for identifying pAKI was at a FENa higher than 0.51 % with a specificity of 72.5% and a sensitivity of 65.0%. In the case of FEK, a value higher than 21.9 % presented the best relation, with a specificity of 67.5% and a sensitivity of 65.0%. CONCLUSIONS: urine biochemistry interpretation in septic patients must be revised. FENa and FEK are related to the severity of AKI and could be helpful complementary tools for diagnosing pAKI.

Prognostic factors associated with advanced chronic kidney disease in a cohort of patients with ANCA vasculitis and renal involvement.

OBJECTIVE: The aim of this study was to evaluate prognostic factors associated with advanced chronic kidney disease (ACKD) in a cohort of patients with ANCA-associated vasculitis and renal involvement. METHODS: Observational retrospective study. We included patients with biopsy-proven ANCA glomerulonephritis (GN) diagnosed between 2001 and 2016, with at least 1-year follow-up. Data were recorded at diagnosis, end of induction, after 12 months of treatment, and at the end of follow-up. We analysed clinical-analytical data and renal histopathology, as well as treatments, dialysis requirement, relapses and death. Univariate analysis was performed to identify factors associated with long-term ACKD (eGFR < 30 ml/min). Multivariate analysis using an alternative outcome (eGFR at the end of follow-up) was performed. Diagnostic accuracy for ACKD of each predictor variable was compared using AUC of ROC curves. RESULTS: Sixty patients were included: 17 GPA, 14 MPA, 5 EGPA, and 24 RLV. Forty-six patients were women (76.7%). Mean age at diagnosis was 67.8 years (SD 13.1), and median follow-up time was 4.2 years (IQR 2.2-6.8). At the end of follow-up, 12 patients (20.0%) had an eGFR < 30 ml/min. Univariate analysis showed a statistically significant association of ACKD with sclerotic class biopsy (OR 7.17, 95% CI 1.34-38.31), 12-month proteinuria (OR 5.16, 95% CI 1.16-22.87), and creatinine at diagnosis (OR 1.24, 95% CI 1.02-1.52), end of induction (OR 15.40, 95% CI 2.41-98.28), and after 12 months (OR 19.25, 95% CI 2.75-134.92). In the multivariate analysis, eGFR at baseline (< 0.001), after 6 months (< 0.001) and 12 months of treatment (< 0.001), remained statistically associated with eGFR at the end of follow-up. The best diagnostic accuracy in ROC curves was shown by serum creatinine at the end of induction treatment (AUC 0.93) and after 12 months (AUC 0.94). CONCLUSION: In this cohort of patients with ANCA GN, creatinine and eGFR at baseline and after 6 and 12 months of treatment were the best predictors of ACKD at the end of follow-up.

Characteristics of acute kidney injury in adult patients with severe COVID-19 / Características de la injuria renal aguda en pacientes adultos con COVID-19 grave

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.

Characteristics of acute kidney injury in adult patients with severe COVID-19.

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.

EPILAT-IRA Study: A contribution to the understanding of the epidemiology of acute kidney injury in Latin America.

INTRODUCTION: Epidemiology of acute kidney injury (AKI) is highly dependent on patient characteristics, context and geography. Considering the limited information in Latin America and the Caribbean, we performed a study with the aim to contribute to improve its better understanding. METHODS: Observational, prospective, longitudinal, multinational cohort study addressed to determine risk factors, clinical profile, process of care and outcomes of AKI in the region. Patients meeting KDIGO AKI definition were included over a 9-month period and designated community or hospital-acquired. De-identified clinical and lab data were entered in a specifically designed on-line platform. Co-variables potentially linked to AKI onset, in-hospital and 90-days mortality, were recorded and correlated using a multiple logistic regression model. RESULTS: Fifty-seven physicians from 15 countries provided data on 905 patients, most with acceptable basic needs coverage. Median age 64 (50-74) yrs; most of them were male (61%) and mestizos (42%). Comorbidities were present in 77%. AKI was community-acquired in 62%. Dehydration, shock and nephrotoxic drugs were the commonest causes. During their process of care, 77% of patients were assessed by nephrologists. Kidney replacement therapy (KRT) was performed in 29% of cases. In-hospital mortality was 26.5% and independently associated to older age, chronic liver disease, hypotension, shock, cardiac disturbances, hospital-acquired sepsis, KRT and mechanical ventilation. At 90-days follow up partial or complete renal recovery was 81% and mortality 24%. CONCLUSIONS: AKI was mainly community-acquired, in patients with comorbidities and linked to fluid loss and nephrotoxic drugs. Mortality was high and long-term follow up poor. Notwithstanding, the study shows partially the situation in the participant countries rather than the actual epidemiology of AKI in Latin America and Caribbean, a pending and needed task.

Rebiopsias en glomerulonefritis asociadas a ANCA: ¿Cuál es su utilidad en la toma de decisiones? / Rebiopsies in ANCA associated glomerulonephritis: What is its use in making decisions?

El objetivo de este estudio fue evaluar la utilidad de la rebiopsia renal en pacientes con glomerulonefritis ANCA en la toma de decisiones. Se incluyeron en forma retrospectiva todos los pacientes con glomerulonefritis ANCA diagnosticados por biopsia renal entre enero de 2002 y mayo de 2017. Se revisó la histología de las rebiopsias y fue correlacionada con los hallazgos clínicos (hematuria, proteinuria y caída del filtrado) y resultados histológicos de la primera y segunda biopsia. Sesenta pacientes (77% mujeres) fueron incluidos. De ellos, 15 (25%) fueron sometidos a una rebiopsia durante el seguimiento. La media de tiempo hasta la rebiopsia fue de 38,4 meses (DS 20,4). En el grupo de rebiopsia, la presencia de hematuria, proteinuria y caída del filtrado glomerular se observó en el 73%, 73% y 60% de pacientes, respectivamente. No encontramos una correlación entre las lesiones activas (semilunas, necrosis) con la presencia de hematuria o caída del filtrado glomerular. En un gran porcentaje, la histología renal mostró progresión en términos de cronicidad y con menor frecuencia lesiones de actividad. A pesar de esto, en el 67% de los pacientes se realizó un cambio de tratamiento, iniciando una nueva terapia de inducción, alcanzando una respuesta renal en el 85% de los casos.

The aim of this study was to evaluate usefulness of renal re-biopsy in patients with ANCA glomerulonephritis in treatment decisions. We included retrospectively all patients with biopsy-proven ANCA glomerulonephritis between January 2002 and May 2017. We analysed patient's baseline characteristics at the time of re-biopsy, presence of microscopic hematuria, proteinuria and/or decline in glomerular filtration rate (GFR) and time to renal relapse/rebiopsy. Data of physicians' decisions after rebiopsy was collected. 60 patients (77% females) were included. Of those, 15 (25%) underwent renal re-biopsy during the follow up based on clinical manifestations. Mean time until re-biopsy was 38.4 months (SD 20.4). In the re-biopsy group, 73% of patients had new onset hematuria, 73% had new onset or worsening proteinuria (40% and 33% respectably), and 60% had decline in the GFR. When analysing histological changes in the repeat biopsy we didn't find a correlation between active lesions (crescents, necrosis etc.) and hematuria. All patients that underwent repeat biopsy were considered to be active but renal histology showed progression in terms of chronicity and rare active histological lesions. Despite this, in 67% of patients, physicians made a treatment change, initiating a new induction therapy regimen and achieving renal response in 85% of patients.

ANCA-associated pauci-immune glomerulonephritis: always pauci-immune?

OBJECTIVES: Anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (GN) is considered "pauci-immune" with absent or mild glomerular tuft staining for immunoglobulin (Ig) and/or complement. However, it is not unusual to see some immune deposits (ID) within glomeruli on immunofluorescence (IF). We determined to evaluate the prevalence and clinical significance of immune deposits in ANCA-associated GN. METHODS: We included all patients with ANCA associated vasculitis with renal biopsies between January 2002 and May 2014: granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, microscopic polyangiitis and renal limited vasculitis. Patients were divided into Group A: biopsy without ID (≤2+ intensity of immunostaining) and Group B: biopsy with ID (>2+ intensity of immunostaining). Serum creatinine, estimated glomerular filtration rate (eGFR) at time of the biopsy, amount of proteinuria and hematuria, requirement of dialysis and extra renal involvement were recorded. RESULTS: Fifty-three patients (75.4% females) were included. Mean age at biopsy was 66.3 years. Typical pauci-immune GN was found in 39 patients (73.5%, group A). In 14 patients (26.4%, group B) examination revealed substantial deposition of Ig or complement in the mesangium and/or along the glomerular capillary wall. The only difference comparing both groups was significantly higher proteinuria in group B (mean 1.6/24 h (SD: 10.7) vs. 0.8/24 h (SD: 7.6), p=0.0036). CONCLUSIONS: In ANCA GN at least a quarter of patients were not "pauci-immune" (26.4%). In this subgroup, immune deposits were only associated with a significantly higher proteinuria. Further basic and clinical research is needed to elucidate the significance of immune deposition in ANCA GN.

Cistatina C como predictor de síndrome cardiorrenal y mal pronóstico en pacientes internados por insuficiencia cardíaca aguda y función renal normal / Cystatin C as Marker of Cardiorenal Syndrome and Poor Prognosis in Patients Hospitalized with Acute Heart Failure and Normal Renal Function

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.