Urine microscopy as a biomarker of Acute Kidney Injury following cardiac surgery with cardiopulmonary bypass / Microscopia urinária como biomarcador de lesão renal aguda após cirurgia cardíaca com circulação extracorpórea

Abstract Introduction: Acute kidney injury (AKI) occurs in about 22% of the patients undergoing cardiac surgery and 2.3% requires renal replacement therapy (RRT). The current diagnostic criteria for AKI by increased serum creatinine levels have limitations and new biomarkers are being tested. Urine sediment may be considered a biomarker and it can help to differentiate pre-renal (functional) from renal (intrinsic) AKI. Aims: To investigate the microscopic urinalysis in the AKI diagnosis in patients undergoing cardiac surgery with cardiopulmonary bypass. Methods: One hundred and fourteen patients, mean age 62.3 years, 67.5 % male, with creatinine 0.91 mg/dL (SD 0.22) had a urine sample examined in the first 24 h after the surgery. We looked for renal tubular epithelial cells (RTEC) and granular casts (GC) and associated the results with AKI development as defined by KDIGO criteria. Results: Twenty three patients (20.17 %) developed AKI according to the serum creatinine criterion and 76 (66.67 %) by the urine output criterion. Four patients required RRT. Mortality was 3.51 %. The use of urine creatinine criterion to predict AKI showed a sensitivity of 34.78 % and specificity of 86.81 %, positive likelihood ratio of 2.64 and negative likelihood ratio of 0.75, AUC-ROC of 0.584 (95%CI: 0.445-0.723). For the urine output criterion sensitivity was 23.68 % and specificity 92.11 %, AUC-ROC was 0.573 (95%CI: 0.465-0.680). Conclusion: RTEC and GC in urine sample detected by microscopy is a highly specific biomarker for early AKI diagnosis after cardiac surgery.

Resumo Introdução: Lesão renal aguda (LRA) ocorre em cerca de 22% dos pacientes submetidos a cirurgia cardíaca e 2,3% necessitam de terapia renal substitutiva (TRS). Os atuais critérios diagnósticos para LRA fundamentados no aumento dos níveis de creatinina sérica apresentam limitações e novos biomarcadores estão sendo testados. O sedimento urinário é um biomarcador que pode ajudar a diferenciar a LRA pré-renal (funcional) da LRA renal (intrínseca). Objetivos: Investigar a urinálise microscópica no diagnóstico de LRA em pacientes submetidos a cirurgia cardíaca com circulação extracorpórea. Métodos: Um total de 114 pacientes com idade média de 62,3 anos, 67,5% do sexo masculino e níveis médios de creatinina de 0,91 mg/dL (DP 0,22) tiveram amostras de urina examinadas nas primeiras 24 horas após a cirurgia. A identificação de células epiteliais tubulares renais (CETR) e cilindros granulares (CG) foi associada a desfechos de desenvolvimento de LRA conforme os critérios do KDIGO. Resultados: Vinte e três pacientes (20,17%) desenvolveram LRA pelo critério de creatinina sérica e 76 (66,67%) pelo critério de diurese. Quatro pacientes necessitaram de TRS. A mortalidade foi de 3,51%. O uso da creatinina urinária como critério preditivo para LRA mostrou sensibilidade de 34,78% e especificidade de 86,81%; razão de verossimilhança positiva de 2,64 e razão de verossimilhança negativa de 0,75; e ASC-COR de 0,584 (IC 95%: 0,445-0,723). Para o critério de diurese, a sensibilidade foi de 23,68% e a especificidade 92,11%; a ASC-COR foi 0,573 (IC 95%: 0,465-0,680). Conclusão: A identificação de CETR e CG em amostras de urina por microscopia representa um biomarcador altamente específico para o diagnóstico precoce de LRA após cirurgia cardíaca.

Urinary semaphorin 3A as an early biomarker to predict contrast-induced acute kidney injury in patients undergoing percutaneous coronary intervention

Contrast-induced acute kidney injury (CI-AKI) is a serious complication of diagnostic coronary angiograph and percutaneous coronary intervention (PCI). However, the exact pathophysiological mechanisms underlying CI-AKI development are largely unknown. The present study examined whether urinary semaphorin 3A levels predict the development of CI-AKI in patients undergoing PCI. This study enrolled 168 patients with stable angina undergoing elective PCI. Serial urine samples, obtained at baseline and 2, 6, 12, 24, 36, and 48 h post-PCI were analyzed by semaphorin 3A and neutrophil gelatinase-associated lipocalin (NGAL) ELISA kit. AKI was defined as an increase in serum creatinine beyond 50% according to the RIFLE classification system. Receiver operator characteristic (ROC) curve analyses identified optimal semaphorin 3A and NGAL values for diagnosing CI-AKI. CI-AKI occurred in 20 of 168 patients. There were no significant differences in the baseline clinical characteristics and angiographic findings between non-AKI patients group and AKI patients group. Both urinary semaphorin 3A and NGAL levels significantly increased at 2 and 6 h post-PCI. ROC analysis showed that the cut-off value of 389.5 pg/mg semaphorin 3A at 2 h post-PCI corresponds to 94% sensitivity and 75% specificity and the cut-off value of 94.4 ng/mg NGAL at 2 h post-PCI corresponds to 74% sensitivity and 82% specificity. Logistic regression showed that semaphorin 3A levels at 2 and 6 h post-PCI were the significant predictors of AKI in our cohort. Urinary semaphorin 3A may be a promising early biomarker for predicting CI-AKI in patients undergoing PCI.

Renal biomarkers of male and female Wistar rats (Rattus norvegicus) undergoing renal ischemia and reperfusion

PURPOSE: To investigate biomarkers of acute renal injury in Wistar rats, subjected to left renal ischemia for 10 minutes, and then compare reperfusion at 24 hours, and at 5, 7, 14 and 21 days after the procedure. METHODS: Eight female and male rats between 60 and 81 days old were used in the Central Animal Facility of the UFMS. Assessed biomarkers included urine protein, urea, creatinine, glucose, sodium, potassium, urine alkaline phosphatase and gamma-glutamyl transferase activities, and protein-to-creatinine ratio; and in serum: urea, creatinine, sodium and potassium, fractional excretion of sodium, potassium, urine flow and creatinine clearance. RESULTS: Greater variance was observed in the parameters at 24 hours and at five days (p<0.05) after reperfusion. On the 21st day, these parameters approximated those obtained for the control group. CONCLUSIONS: Renal ischemia for 10 minutes was sufficient to raise urine levels of protein, glucose, fractional excretion of potassium, urea, creatinine clearance, urine activity of gamma-glutamyltransferase and alkaline phosphatase enzymes in the first 24 hours, up to five days after reperfusion, which may indicate risk of acute kidney injury, according to the RIFLE classification. .

NGAL urinária em pacientes sem e com lesão renal aguda em unidade de terapia intensiva / Urinary NGAL in patients with and without acute kidney injury in a cardiology intensive care unit

Objetivo: Avaliar a eficácia diagnóstica e prognóstica da lipocalina associada à gelatinase neutrofílica urinária em pacientes de unidade de terapia intensiva. Métodos: Estudo do tipo coorte, prospectivo, longitudinal desenvolvido em uma unidade de terapia intensiva clínica especializada em cardiologia. Os pacientes foram estratificados segundo os grupos sem e com lesão renal aguda, acompanhados a partir das primeiras 24 horas de internação até a alta hospitalar ou óbito. A creatinina sérica, o fluxo urinário e a lipocalina associada à gelatinase neutrofílica urinária foram coletadas em dois períodos: 24 horas e 48 horas de admissão. Resultados: Foram avaliados 83 pacientes clínicos da unidade de terapia intensiva, com predomínio do gênero masculino (57,8%). Os pacientes foram agrupados em sem lesão renal aguda (N=18), com lesão renal aguda (N=28) ou com lesão renal aguda grave (N=37). Entre os pacientes com lesão renal aguda e lesão renal aguda grave, foram prevalentes os portadores de doenças crônicas, em uso de ventilação mecânica e em terapia de substituição renal, além daqueles com maiores taxas de permanência na unidade de terapia intensiva e hospitalar, e maior mortalidade. O grupo com lesão renal aguda não apresentou alteração significativa da creatinina sérica nas primeiras 24 horas na unidade de terapia intensiva, ...

Objective: To assess the diagnostic and prognostic efficacy of urine neutrophil gelatinase-associated lipocalin in patients admitted to an intensive care unit. Methods: Longitudinal, prospective cohort study conducted in a cardiology intensive care unit. The participants were divided into groups with and without acute kidney injury and were followed from admission to the intensive care unit until hospital discharge or death. Serum creatinine, urine output and urine neutrophil gelatinase-associated lipocalin were measured 24 and 48 hours after admission. Results: A total of 83 patients admitted to the intensive care unit for clinical reasons were assessed, most being male (57.8%). The participants were divided into groups without acute kidney injury (N=18), with acute kidney injury (N=28) and with severe acute kidney injury (N=37). Chronic diseases, mechanical ventilation and renal replacement therapy were more common in the groups with acute kidney injury and severe acute kidney injury, and those groups exhibited longer intensive care unit stay and hospital stay and higher mortality. Serum creatinine did not change significantly in the group with acute kidney injury within the first 24 hours of admission to the intensive care unit, although, urine neutrophil gelatinase-associated lipocalin was high in the groups with acute kidney injury and severe acute kidney injury (p<0.001). Increased urine neutrophil gelatinase-associated lipocalin was associated with death. ...

Papel da lipocalina associada à gelatinase neutrofílica (NGAL) urinária na nefrotoxicidade da cisplatina em pacientes com câncer de cabeça e pescoço / Evaluation of the cisplatin nephrotoxicity using the urinary neutrophil gelatinase-associated lipocalin (NGAL) in patients with head and neck cancer

Introdução: A injúria renal aguda (IRA) em pacientes que recebem a cisplatina é comum, portanto, a avaliação da função renal em pacientes utilizando drogas nefrotóxicas é fundamental. Objetivo: Avaliar a incidência da IRA e o papel da lipocalina associada à gelatinase neutrofílica (NGAL) na avaliação da função renal em pacientes com câncer de cabeça e pescoço (CCP) que receberam a cisplatina. Métodos: Foram avaliados prospectivamente 50 pacientes com CCP, tratados com três sessões de cisplatina. Foram coletados sangue e urina 24 horas antes da cisplatina, 24 horas após a infusão, 48 horas após cada aplicação e 35 dias após o término do tratamento (NGAL urinária, proteína C reativa, creatinina e taxa de filtração glomerular, desidrogenase lática e magnésio plasmáticos). Resultados: A IRA foi observada em 78% dos pacientes. Houve aumento na creatinina, ureia e queda na TFG após cada ciclo de cisplatina, e aumento da NGAL urinária. Foi observada associação positiva entre os níveis de NGAL e a creatinina e PCR. Evidenciou-se um aumento dos níveis de creatinina, NGAL, PCR e diminuição da TFG nos pacientes com IRA em relação aos pacientes sem IRA. Conclusão: Observamos IRA em 78% dos pacientes avaliados com CCP tratados com a cisplatina e correlação da NGAL com a creatinina e a TFG em demonstrar lesão renal. Os níveis de NGAL podem estar elevados em relação aos níveis basais, mesmo antes da utilização da cisplatina. .

Introduction: Acute kidney injury (AKI) in patients receiving cisplatin is common, therefore the evaluation of renal function in patients on use of nephrotoxic drugs is fundamental. Objective: To evaluate the incidence of AKI and the role of lipocalin associated to neutrophil gelatinase (NGAL) in the monitoring of renal function in patients with head and neck cancer (HNC) who received cisplatin. Methods: We prospectively studied 50 patients with HNC treated with three sessions of cisplatin. Blood and urine were collected 24 hours before cisplatin, 24 hours after infusion, 48 hours after each application and 35 days after the end of treatment (urine NGAL, C-reactive protein, creatinine, glomerular filtration rate, plasma lactate dehydrogenase and magnesium). Results: AKI was observed in 78% of patients. There was increase in creatinine, and decrease in GFR after each cycle of cisplatin, and increased urine NGAL. Positive association was observed between the levels of NGAL, creatinine and C-reactive protein. It was observed an increase in creatinine, NGAL, C-reactive protein and decreased GFR in AKI patients compared to patients without AKI. Conclusion: AKI was noted in 78% of patients with HNC treated with cisplatin and showed the correlation of NGAL with creatinine and GFR in demonstrating renal injury. NGAL levels may be elevated compared to baseline levels, even before the use of cisplatin. .

Lesión renal aguda secundaria a lisis tumoral inducida por esteroides en una adolescente con leucemia linfoblástica aguda: Rol de la alcalinización urinaria y diálisis peritoneal / Acute kidney injury secondary to steroid-induced tumor lysis in an adolescent with acute lymphoblastic leukemia: Role of urinary alkalinisation and peritoneal dialysis

Una adolescente con leucemia linfoblástica aguda desarrolló un síndrome de lisis tumoral precoz y grave con lesión renal aguda luego de una dosis única y baja de esteroides. La disfunción renal se atribuyó primariamente a una nefropatía por fosfato con nefrocalcinosis debido a elevaciones extremas de este componente en sangre. La alcalinización urinaria probablemente contribuyó a su patogenia. Se utilizó diálisis peritoneal con resolución de la nefrocalcinosis y normalización de la depuración de creatinina.

An adolescent with acute lymphoblastic leukemia developed an early and severe tumor lysis syndrome with acute kidney injury after a low and single dose of steroids. Renal dysfunction was attributed primarily to phosphate nephropathy with nephrocalcinosis due to extreme elevations of phosphate in blood. Urinary alkalinization probably contributed to this development. We used peritoneal dialysis with resolution of nephrocalcinosis and normalization of creatinine clearance.

Diagnóstico temprano de la insuficiencia renal aguda con la determinación de las fracciones de excreción en pacientes críticos en la UCI / Early diagnosis of acute renal failure with fractional excetion determnation in critical patients at intensive cara unit

Antecedentes: la insuficiencia renal aguda (IRA) es una afección clínica observada con frecuencia en las unidades de cuidados intensivos (UCI), reportándose en 5 por ciento de los ingresos: Objetivo: encontrar una prueba para establecer el diagnóstico temprano de IRA, que sea confiable, segura, accesible y que no se modifique con el manejo. Material y métodos: se incluyeron 28 pacientes con IRA (18 hombres y 10 mujeres), con edad promedio de 55.5 años. Los factores de riesgo fueron: choque hipovolémico, ocho pacientes; sepsis, cinco, hepatopatía, dos, pancreatitis, tres; cardiopatías seis: toxemia gravídica, cuatro. Se formaron dos grupos: uno con 18 pacientes que evolucionaron a IRA y el otro con 10 que no la presentaron. Se determinó la fracción excretada de sodio (FeNa), fracción excretada de potasio (FeK), depuración de creatinina (DepCr), depuración de agua libre (Dep H2O) y se cuantificó el volumen urinario/minuto a las 6, 24 y 48 h del episodio predisponente. Se compararon ambos grupos utilizando análisis de varianza de un factor para cada tiempo del estudio. Resultados: hubo diferencias significativas en la Dep H2O (p < 0.03) en las primeras 6h. Al comparar ambos grupos sólo se encontraron diferencias significativas en FeK a las 48 h y después de 6h en DepCr. Conclusiones: la prueba de mayor utilidad para el diagnóstico temprano de IRA es la depuración de agua libre

Ras oncoprotein level and urinary enzymes activity as sensitive indicators of renal injury in acute and chronic renal failure

Sixty-one patients with renal failure and ten healthy controls were included in this study. Patients were subdivided into three groups; group I included 20 patients with acute renal failure [ARF], group II included 20 patients with chronic renal failure [CRF] and group III included 21 patients with renal impairment [RI]. Serum ras oncoprotein was significantly higher in patients with ARF, CRF and RI compared with the controls. Ras oncoprotein level, sialic acid level and urinary excretion of the studied enzymes were not changed significantly with increased degrees of albuminuria or with the presence of casts, RBCs or pus cells in urine. Neither kidney size sonographically nor degree of echogenicity has an effect on the studied bioindices. The study revealed statistically significant correlations between ras oncogene expression and urinary enzymes excreted during renal damage

Depuración de creatinina en orina de dos horas en pacientes en estado crítico / Creatinine clearance in urine samples of two hours in critically ill patients

El diagnóstico temprano de insuficiencia renal aguda permite al clínico llevar a cabo las medidas necesarias y oportunas para corregir la función renal. Esto es extremadamente importante para los enfermos en estado crítico, quienes frecuentemente son agredidos con drogas nefrotóxicas y que cursan con estado hemodinámicos que deterioran la función renal. La depuración de creatinina en recolecciones de orina de dos horas es tan efectiva como la calculada de recolecciones más prolongadas; con la ventaja de que puede llevarse a cabo con mayor frecuencia, brindando información del funcionamiento renal desde las primeras horas del ingreso de los pacientes a la Unidad de Cuidados Intensivos. En este estudio se realizaron cálculos de depuración de creatinina en 28 pacientes por recolecciones de orina de dos horas, comparándose con las recolecciones de orina de 24 horas de cada paciente, obteniéndose una correlación significativa (r=0.966). Concluimos que la depuración de creatinina en orina de dos horas es equiparable a la calculada en muestras de orina de 24 horas cuando los pacientes tienen por lo menos 15 ml/hora de diuresis

La filtración glomerular: un análisis para su medición e interpretación / Glomerular filtration: an analysis to its medition and interpretation

La depuración de creatinina o "clearence" de creatinina, se ha venido utilizando desde hace más de 50 años para medir la velocidad de filtración glomerular, y de esta manera determinar el nivel de funcionamiento renal. Sin embargo, debe tomarse en cuenta que este método sobre estima en un 30 a 60// la verdadera velocidad de filtración glomerular, por lo que analizamos en el presente artículo las fórmulas de Cockcrofty Gault, Jardmy Effersoe y Rojer Jellife, las cuales pueden ser utilizadas con buena aceptación para analizar este parámetro en pacientes críticos

Urinary diagnostic indices in the management of leptospirosis: selection of patients for dialysis therapy

Cases of leptospirosis admitted to the Queen Elizabeth Hospital (QEH), Barbado, were assessed for the presence of "pre-renal azotaemia" (NON-ARF) as opposed to "acute renal failure" (ARF). Distinction between the two diagnoses was made on the basis of clinical course. Peritoneal dialysis was inappropriately utilised in 26% of patients receiving such therapy. This study evaluates diagnóstic tests for pre-renal azotaemia, and acute renal failure in leptospsirosis, and indicates guidelines for the management of azotaemia in such patientes. U/P urea and osmolar ratios show high sensitivity in diagnosing pre-renal azotaemia. While "early" dialysis is essential for patients with acute leptospiral renal failure, in those with plasma creatinines less than 600 micronmol/litre on entry and indices indicating NON-ARF, decisions regarding dialysis con safely be delayed for 48-72 hours while the effect of rehydration is assessed