Predictive Value of Proteinuria in Adult Dengue Severity

Abstract

BackgroundDengue is an important viral infection with different presentations. Predicting disease severity is important in triaging patients requiring hospital care. We aim to study the value of proteinuria in predicting the development of dengue hemorrhagic fever (DHF), utility of urine dipstick test as a rapid prognostic tool.Methodology and principal findingsAdult patients with undifferentiated fever (n = 293) were prospectively enrolled at the Infectious Disease Research Clinic at Tan Tock Seng Hospital, Singapore from January to August 2012. Dengue infection was confirmed in 168 (57%) by dengue RT-PCR or NS1 antigen detection. Dengue cases had median fever duration of 6 days at enrolment. DHF was diagnosed in 34 cases according to the WHO 1997 guideline. Dengue fever (DF) patients were predominantly younger and were mostly seen in the outpatient setting with higher platelet level. Compared to DF, DHF cases had significantly higher peak urine protein creatinine ratio (UPCR) during clinical course (26 vs. 40 mg/mmol; p<0.001). We obtained a UPCR cut-off value of 29 mg/mmol based on maximum AUC in ROC curves of peak UPCR for DF versus DHF, corresponding to 76% sensitivity and 60% specificity. Multivariate analysis with other readily available clinical and laboratory variables increased the AUC to 0.91 with 92% sensitivity and 80% specificity. Neither urine dipstick at initial presentation nor peak urine dipstick value during the entire illness was able to discriminate between DF and DHF.ConclusionsProteinuria measured by a laboratory-based UPCR test may be sensitive and specific in prognosticating adult dengue patients.

Retrospective analysis of biochemical profile of dengue infection in a tertiary care hospital

“…In a study by Vasanwala et al concluded that urine protein creatinine ratio done at onset and around the time before fever subsided predicted the likelihood of developing dengue hemorrhagic fever. 9 In a report by Mendez et al it was shown that the incidence of proteinuria in dengue was 62% which was comparable to our study.…”

Endothelial cells in dengue hemorrhagic fever

“…(Bethell et al, 2001; Vasanwala et al, 2014; Wills et al, 2004) This is consistent with the elevated extracellular water observed during defervescence in patients with DHF in comparison to patients with DF(Libraty et al, 2002b) Increased urinary excretion of small protein molecules such as albumin and transferrin was elevated during shock phase in severe dengue cases in comparison to the excretion rate measured after recovery(Vasanwala et al, 2014; Wills et al, 2004) In addition, increased heparin sulfate urinary excretion was also observed. Although glomerular vascular bed is not the major site where leakage occurs in DHF, these findings may reflect the perturbation of vascular permeability regulation that occurs at other anatomical sites such as the pleural and abdominal cavities.…”

Manifestaciones del dengue a nivel renal

“…La hipoalbuminemia y proteinuria son bien reconocidos en la infección por dengue. Esto se cree se debe a la alteración de la filtración alterada por alteración del glicocálix, como el virus del dengue y NS1 son conocidos por unirse a sulfato de heparán, que es parte de la glicocálix [27][28] . La infección por dengue ha sido asociada con una variedad de desórdenes renales: injuria renal aguda, proteinuria, hematuria y glomerulonefritis han sido reportadas durante o poco tiempo después de la infección 29 .…”

“…Los pacientes con dengue leve tuvieron proteinuria significativamente más bajos que los pacientes con dengue hemorrágico inminente y choque por dengue. El seguimiento diario en este estudio prospectivo permitió determinar el valor discriminatorio de proteinuria, que no fue evidente en el período febril temprano pero sí entre los días 4 y 7, justo antes de desaparición de la fiebre y coincidente con la fuga plasmática 27 . Se llegaría así a la conclusión de que la aparición y el pico de proteinuria mediante una prueba UPCR basada en el laboratorio se asocia significativamente con el desarrollo posterior de dengue hemorrágico, ya sea en ambulatorios u hospitalizados.…”

“…Se llegaría así a la conclusión de que la aparición y el pico de proteinuria mediante una prueba UPCR basada en el laboratorio se asocia significativamente con el desarrollo posterior de dengue hemorrágico, ya sea en ambulatorios u hospitalizados. El dosaje diario de UPCR puede ser una herramienta de pronóstico útil, sensible y específico en relación con otros parámetros clínicos para ayudar en el triaje de aquellos que requieren atención hospitalaria 27 . Cabe destacar que, utilizando UPCR ajustada por edad y día de enfermedad, tuvo una sensibilidad de 76% y especificidad de 77% para predecir el dengue hemorrágico, mientras que la combinación con recuento de glóbulos blancos, hematocrito sérico, recuento de plaquetas, proteínas séricas y sangrado tuvo una sensibilidad de 92% y especificidad de 80%.…”