The relationship of oleic acid/albumin molar ratio and clinical outcomes in leptospirosis

Abstract

Human leptospirosis is an acute infectious zoonosis presenting specific lipid disorders. Previous in vitro studies showed both leptospira glycolipoprotein endotoxin, and high oleic acid levels were associated with Na/K-ATPase inhibition that is amplified by the reduction of circulating albumin levels. In this study, we aimed to investigate the relationship of oleic acid/albumin (OA/A) molar ratio and clinical outcomes in Leptospirosis. Through a prospective observational cohort study employing high-performance liquid chromatography (HPLC) we sequentially determined serum concentrations of nonesterified fatty acids (NEFA) and albumin in twenty-eight patients with severe leptospirosis since their hospital admission. Twenty patients recovered, and eight died. Data was distributed in two groups according to clinical outcomes. Oleic acid/albumin molar ratios (OA/A), initial samples, were higher than those in healthy donors. The ratio OA/A, however, persisted high in dying patients, whereas patients who survived had a reduction matching to healthy donors. Biochemical alterations suggest that cure is correlated to the reestablishment of the OA/A molar ratio, while fatal outcomes related to persisting OA/A imbalances. Analysis by receiver operating characteristic (ROC) showed the area under the curve of 0.864 and the cutoff value of 0.715 being associated with a high odds ratio. Lipid analysis from patients with leptospirosis had an acute high serum OA/A molar ratio, and sustained imbalance has a high odds ratio and strong correlation with mortality.

Keywords: Acute lipotoxicity; Leptospirosis clinical outcome; Lipidome; Na/K-ATPase; Oleic acid/albumin.

Figure 1

Oleic acid/albumin molar ratios by group: An analysis by the multiple Tukey-Kramer test. Oleic acid/albumin molar ratios at two time points: (A) at hospital admission: Group 1 (1.32 ± 0.39) and Group 2 (1. 41 ± 0.89) were significantly different from control (0,037 ± 0,058), with q = 6.412 (CI: -1.509 -0.45050) and q = 5.716 (CI: -1.718 -0.4216), respectively; p < 0.01. The groups 1 and 2 were not statistically significant q = 0.5150 (CI: -0.6619 0.4819). (B) Before hospital discharge: Group 1 (0.44 ± 0.58) and control (0.037 ± 0.058) were significantly different from Group 2 (1.48 ± 0.8) with q = 5.638 (-1.550 -0.3701) and q = 5.490 (-1.729 -0.3911), respectively; p < 0.01. When Group 1 and 2 were compared q = 0.643 (CI: -0.6461 to 0.4461); and p < 0.01. Individualized patients are showed in Figures 1C and 1D.

Figure 2

Serum albumin levels by the Multiple Tukey-Kramer test. (A) At hospital admission: Groups 1 (416 ± 164 μM) and 2 (334 ± 159 μM) both were significantly different from controls (691 ± 34 μM), p < 0.001 with q = 7.165 (CI: -407. 95 to -142.05) and 7.595 (CI: -357 to -519), respectively. When comparing groups 1 and 2, q = 1.978 (CI: -61.604 to -225.60); p > 0.05. (B) At the time of hospital discharge or prior to death: Group 1 (342 ± 156 μM) and Group 2 (343 ± 179 μM), presented p < 0.001 compared to controls (691 ± 34 μM) with q = 9.030 (CI: -482.88 to -215.12) and q = 7.352 (CI: -511.97 to -184.03), respectively; when compared, groups 1 and 2 showed q = 0.02395 (CI:-145.61 to 143.61), respectively; p > 0.05.

Figure 3

Deming Regression of Oleic Acid/Albumin molar ratios of patients through hospitalization time according to prognosis: Although OA/A of patients over time were different (the patients who died were hospitalized for a shorter time), we observed a statistically significant decrease in OA/A ratio over time in group 1, which did not occur in group 2. Group 1: F = 443057.62, (CI: -0.1511 to -0.003701), p < 0.05 and Group 2: F = 0.5782, (CI: -0.1209 to 0.02459).

Figure 4

ROC curve for serum oleic acid/albumin molar ratios from leptospirosis patients according to the clinical outcome: AUC of 0.8684 (CI: 0.689 to 1.047); p = 0.0029 (A) and ROC curve with reference line (B).

Figure 5

Linear Regression Oleic/Albumin molar ratio during hospitalization. The linear regression was made comparing oleic acid/albumin molar ration to two outcomes discharge (cure) or death. Molar ration from discharge patients present statistical difference with P value 0.0171.