ABSTRACT
INTRODUCTION: During the pandemic caused by the SARS-CoV-2 virus, some patients who develop severe forms of COVID-19 present thrombotic microangiopathy in the course of the disease's clinical progression. METHODS: Data came from direct patient observation and clinical records. We performed a kidney biopsy and used optical microscopy and immunofluorescence techniques. RESULTS: We present the case of a 78-year-old male patient, mestizo, overweight with a history of high blood pressure, ischemic cardiopathy and chronic obstructive pulmonary disease who was first admitted to the hospital due to respiratory symptoms and diarrhea related to COVID-19, from which he recovered. He was subsequently readmitted with symptoms of acute renal dysfunction accompanied by mild anemia and thrombocytopenia; at the same time, he resulted negative for COVID-19 via a real-time polymerase chain reaction test. A kidney biopsy revealed thrombi in glomerular capillaries, acute tubular necrosis, thickening of extraglomerular blood vessel walls, and C3 deposits in the glomerular tufts. CONCLUSIONS: We describe a case of thrombotic microangiopathy with kidney biopsy in a patient recovering from COVID-19. Acute renal dysfunction is a form of thrombotic microangiopathy that has been observed in patients recovering from COVID-19.
Subject(s)
COVID-19 , Thrombotic Microangiopathies , Aged , Cuba , Humans , Kidney , Male , SARS-CoV-2 , Thrombotic Microangiopathies/diagnosis , Thrombotic Microangiopathies/etiologyABSTRACT
Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disease characterized by an overexpression of epidermal growth factor receptor (EGFR). Nimotuzumab is a recombinant humanized monoclonal antibody against human EGFR. The aim of this study was to develop a population pharmacokinetic model for nimotuzumab and to identify demographic and clinical predictive factors of the pharmacokinetic variability. The population pharmacokinetics (PopPK) of nimotuzumab was characterized using a nonlinear mixed-effect modeling approach with NONMEM®. A total of 422 log-transformed concentration-versus-time datapoints from 20 patients enrolled in a single-center phase I clinical trial were used. Quasi steady state approximation of the full TMDD (target-mediated drug disposition) model with constant target concentration best described the concentration-time profiles. A turnover mediator was included which stimulates the non-specific clearance of mAb in the central compartment in order to explain the reduced levels at higher doses. Covariates had no influence on the PK (pharmacokinetics) parameters. The model was able to detect that the maximum effective dose in ADPKD subjects is 100 mg. The developed PopPK model may be used to guide the dose selection for nimotuzumab during routine clinical practice in patients with polycystic kidney disease. The model will further support the ongoing investigations of the PK/PD relationships of nimotuzumab to improve its therapeutic use in other disease areas.
ABSTRACT
INTRODUCCIÓN: la hipercalciuria constituye el principal trastorno metabólico en la litiasis urinaria. Su diagnóstico implica recolección de orina de 24 horas con riesgo de errores y se ha utilizado el índice calcio creatinina como marcador de hipercalciuria. OBJETIVOS: determinar la validez de este indicador como marcador de hipercalciuria. MÉTODOS: se realizó un estudio descriptivo, transversal por la importancia del diagnóstico de la hipercalciuria y los desacuerdos en la utilidad del índice calcio creatinina y su punto de corte óptimo. Se estudiaron 1603 sujetos litiásicos cubanos entre 2 y 19 años, a los que se les mensuró calciuria de 24 horas e índice calcio creatinina de la segunda orina de la mañana. RESULTADOS: se obtuvo correlación positiva moderada entre las variables. Para los valores de corte tradicionales del índice calcio creatinina, la sensibilidad fue 95,7 % y 81,9 %, y la especificidad 48,3 % y 66,7 %, para niños y adolescentes, respectivamente. CONCLUSIONES: el índice calcio creatinina es útil como prueba de despistaje poblacional de hipercalciuria, sin embargo para la confirmación diagnóstica se requiere ineludiblemente la mensuración de la calciuria por recolección de orina de 24 horas.
INTRODUCTION: hypercalciuria is the main metabolic disorder in urolithiasis. Diagnosis involves collecting urine for 24 hours with risk of errors and calcium creatinine ratio has been used as a marker of hypercalciuria. OBJECTIVES: determine the validity of this indicator as a hypercalciuria marker. METHODS: a cross-sectional descriptive study was conducted due to the importance of the diagnosis of hypercalciuria and disagreements on the utility of calcium creatinine ratio and optimal cutoff. 1603 Cuban lithiasic subjects were studied. Their age ranged between 2 and 19 years. 24 hour urinary calcium and calcium- creatinine ratio of the second morning urine were studied. RESULTS: moderate positive correlation between variables was obtained. For values of traditional cutting of calcium creatinine ratio, sensitivity was 95.7% and 81.9%, and specificity 48.3% and 66.7% for children and adolescents, respectively. CONCLUSIONS: calcium creatinine ratio is useful as evidence of population screening for hypercalciuria, however for diagnostic confirmation the measurement of urinary calcium is inevitably required by collecting urine for 24 hours.
Subject(s)
Humans , Child , Adolescent , Creatinine , Hypercalciuria/diagnosis , Epidemiology, Descriptive , Cross-Sectional Studies/methodsABSTRACT
Introducción: la hipercalciuria constituye el principal trastorno metabólico en la litiasis urinaria. Su diagnóstico implica recolección de orina de 24 horas con riesgo de errores y se ha utilizado el índice calcio creatinina como marcador de hipercalciuria. Objetivos: determinar la validez de este indicador como marcador de hipercalciuria. Métodos: se realizó un estudio descriptivo, transversal por la importancia del diagnóstico de la hipercalciuria y los desacuerdos en la utilidad del índice calcio creatinina y su punto de corte óptimo. Se estudiaron 1603 sujetos litiásicos cubanos entre 2 y 19 años, a los que se les mensuró calciuria de 24 horas e índice calcio creatinina de la segunda orina de la mañana. Resultados: se obtuvo correlación positiva moderada entre las variables. Para los valores de corte tradicionales del índice calcio creatinina, la sensibilidad fue 95,7 por ciento y 81,9 por ciento, y la especificidad 48,3 por ciento y 66,7 por ciento, para niños y adolescentes, respectivamente. Conclusiones: el índice calcio creatinina es útil como prueba de despistaje poblacional de hipercalciuria, sin embargo para la confirmación diagnóstica se requiere ineludiblemente la mensuración de la calciuria por recolección de orina de 24 horas(AU)
Introduction: hypercalciuria is the main metabolic disorder in urolithiasis. Diagnosis involves collecting urine for 24 hours with risk of errors and calcium creatinine ratio has been used as a marker of hypercalciuria. Objectives: determine the validity of this indicator as a hypercalciuria marker. Methods: a cross-sectional descriptive study was conducted due to the importance of the diagnosis of hypercalciuria and disagreements on the utility of calcium creatinine ratio and optimal cutoff. 1603 Cuban lithiasic subjects were studied. Their age ranged between 2 and 19 years. 24 hour urinary calcium and calcium- creatinine ratio of the second morning urine were studied. Results: moderate positive correlation between variables was obtained. For values of traditional cutting of calcium creatinine ratio, sensitivity was 95.7 percent and 81.9 percent, and specificity 48.3 percent and 66.7 percent for children and adolescents, respectively. Conclusions: calcium creatinine ratio is useful as evidence of population screening for hypercalciuria, however for diagnostic confirmation the measurement of urinary calcium is inevitably required by collecting urine for 24 hours(AU)
