Endothelial Glycocalyx Damage is Associated with Leptospirosis Acute Kidney Injury

Libório, Alexandre Braga; Braz, Marcelo Boecker Munoz; Seguro, Antônio Carlos; Meneses, Gdayllon Cavalcante; Neves, Fernanda Macedo de Oliveira; Pedrosa, Danielle Carvalho; Cavalcanti, Luciano Pamplona de Góes; Martins, Alice Maria Costa; Daher, Elizabeth De Francesco

doi:10.4269/ajtmh.14-0232

Cited by 44 publications

(40 citation statements)

References 24 publications

(29 reference statements)

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“…The increased level of sICAM-1 is consistent with previous results of the Thai patients [16] and of a study performed on 46 patients during a leptospirosis outbreak in Brazil [15]. Our results indicated values 3 times superior to the two previous studies.…”

Section: Discussionsupporting

confidence: 92%

“…The expression of soluble adhesion molecules has been extensively analyzed in the setting of sepsis and septic shock as biological prognosis markers [14] but little is known in the context of human leptospirosis and as discussed later [15–17]. We were interested to evaluate the levels of several soluble adhesion molecules during the course of hospitalized cases of leptospirosis.…”

Section: Introductionmentioning

confidence: 99%

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Increased levels of soluble forms of E-selectin and ICAM-1 adhesion molecules during human leptospirosis

et al. 2017

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Leptospirosis is a multisystemic zoonotic disease with infiltration of visceral organs by Leptospira. The capacity of the vascular endothelium to grant immune cell recruitment and activation in target organs during the disease course remains poorly characterized. We ascertained the levels of expression of several soluble cell adhesion molecules (CAM) notably expressed by endothelial cells in human leptospirosis. We prospectively enrolled 20 hospitalized patients and compared them to 10 healthy controls. Disease severity was defined by one or more organ failures, or death. Plasmatic concentrations of soluble CAM were assessed by multiplex bead assay at the time of patient presentation (M0) and 1 month after hospital discharge. The levels of soluble E-selectin (sCD62E) and soluble intercellular adhesion molecule 1 (sICAM-1, sCD53) were significantly increased in patients compared to controls (p<0.0001) and at 1 month (p<0.0001) with median values at 978 ng/ml (interquartile ranges 787–1164; sCD62E) and 1021 ng/ml (690–1428; sCD53). At M0, Soluble P-selectin level (sCD62P) was found to be decreased with levels at 60 ng/ml (0–631) versus 711 ng/ml (343–1113) for healthy controls (p<0.05). Levels of sICAM-3 (sCD50), sVCAM-1 (vascular cell adhesion molecule, sCD106) and sPECAM-1 (platelet endothelial cell adhesion molecule, sCD31) were not different from healthy subjects at M0. This study shows that two adhesion molecules, shed as soluble forms, are elevated during the acute phase of leptospirosis: E-selectin and s-ICAM1. These molecules may interfere with the process of immune cell recruitment to clear Leptospira at tissue levels.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Increased levels of soluble forms of E-selectin and ICAM-1 adhesion molecules during human leptospirosis

et al. 2017

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“…The uDA1/Cr level was correlated with the level of uNGAL/Cr, which is a 25 kDa member of the lipocalin protein family that was first identified in activated human neutrophils [18], and also with the levels of uNAG/Cr, a lysosomal enzyme abundant in proximal kidney tubule cells. An increase of uNAG levels and tubular dysfunction in leptospirosis patients was reported previously [19], and serum and urine NGAL has been shown to be associated with acute kidney failure [12,20]. However, it has also been reported that urinary tract infections such as cystitis are also associated with uNGAL levels in the absence of AKI, as neutrophils secrete NGAL [21,22].…”

Section: Discussionmentioning

confidence: 76%

Urine Levels of Defensin α1 Reflect Kidney Injury in Leptospirosis Patients

Chagan-Yasutan

Chen

Lacuesta³

et al. 2016

IJMS

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Leptospirosis is a zoonotic disease whose severe forms are often accompanied by kidney dysfunction. In the present study, urinary markers were studied for potential prediction of disease severity. Urine samples from 135 patients with or without leptospirosis at San Lazaro Hospital, the Philippines, were analyzed. Urine levels of defensin α1 (uDA1) were compared with those of neutrophil gelatinase-associated lipocalin (uNGAL) and N-acetyl-β-d-glucosidase (uNAG). Serum creatinine (Cr) was used as a marker of kidney injury. The levels of uDA1/Cr, uNGAL/Cr, and uNAG/Cr were positive in 46%, 90%, and 80% of leptospirosis patients, and 69%, 70%, and 70% of non-leptospirosis patients, respectively. In leptospirosis patients, the correlation of uDA1/Cr, uNGAL/Cr and uNAG/Cr levels with serum Cr were r = 0.3 (p < 0.01), r = 0.29 (p < 0.01), and r = 0.02 (p = 0.81), respectively. uDA1/Cr levels were correlated with uNGAL/Cr levels (r = 0.49, p < 0.01) and uNAG/Cr levels (r = 0.47, p < 0.0001) in leptospirosis patients. These findings suggest that uDA1, uNGAL, and uNAG were elevated in leptospirosis patients and reflected various types of kidney damage. uDA1 and uNGAL can be used to track kidney injury in leptospirosis patients because of their correlation with the serum Cr level.

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“…1,15,20,21,162 Although results from biopsy series are likely confounded by indication bias, those studies suggest that the role of a renal biopsy must be reconsidered in the diagnosis and management of AKI of unclear etiology, such as: unexplained AKI; acute interstitial nephritis 60,163,164 acute or chronic glomerulonephritis, or rapidly progressive glomerulonephritis 165 ; interstitial or tubular injury due to drug toxicity, or exposure to traditional herbal remedies 21,166–170 ; thrombotic microangiopathies 171 ; or leptospirosis. 172–176 …”

Section: Histopathology In Akimentioning

confidence: 99%

Acute Kidney Injury Recognition in Low- and Middle-Income Countries

Cerdá

Mohan

Garcia-Garcia

et al. 2017

Kidney International Reports

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Acute kidney injury (AKI) is increasingly common around the world. Because of the low availability of effective therapies and resource limitations, early preventive and therapeutic measures are essential to decrease morbidity, mortality, and cost. Timely recognition and diagnosis of AKI requires a heightened degree of suspicion in the appropriate clinical and environmental context. In low- and middle-income countries (LMICs), early detection is impaired by limited resources and low awareness. In this article, we report the consensus recommendations of the 18th Acute Dialysis Quality Initiative meeting in Hyderabad, India, on how to improve recognition of AKI. We expect these recommendations will lead to an earlier and more accurate diagnosis of AKI, and improved research to promote a better understanding of the epidemiology, etiology, and histopathology of AKI in LMICs.

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Endothelial Glycocalyx Damage is Associated with Leptospirosis Acute Kidney Injury

Cited by 44 publications

References 24 publications

Increased levels of soluble forms of E-selectin and ICAM-1 adhesion molecules during human leptospirosis

Increased levels of soluble forms of E-selectin and ICAM-1 adhesion molecules during human leptospirosis

Urine Levels of Defensin α1 Reflect Kidney Injury in Leptospirosis Patients

Acute Kidney Injury Recognition in Low- and Middle-Income Countries

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