Plasma Osteopontin Levels is Associated with Biochemical Markers of Kidney Injury in Patients with Leptospirosis

Abstract

: Leptospirosis becomes severe, with a fatality rate of >10%, and manifests as severe lung injury accompanied by acute kidney injury. Using urine and blood samples of 112 patients with leptospirosis, osteopontin (OPN), galectin-9 (Gal-9) and other kidney-related biomarkers were measured to understand the pathological and diagnostic roles of OPN and Gal-9 in leptospirosis. Plasma levels of full-length (FL)-OPN (pFL-OPN) (p < 0.0001), pFL-Gal-9(p < 0.0001) and thrombin-cleaved OPN (p < 0.01) were significantly higher in patients with leptospirosis than in healthy controls (n = 30), as were levels of several indicators of renal toxicity: serum cystatin C (p < 0.0001), urine N-acetyl-β-glucosaminidase (NAG)/creatinine (p < 0.05), and urine clusterin/creatinine (p < 0.05). pFL-Gal-9 levels were negatively correlated with pFL-OPN levels (r = −0.24, p < 0.05). pFL-OPN levels were positively correlated with serum cystatin C (r = 0.41, p < 0.0001), urine NAG/creatinine (r = 0.35, p < 0.001), urine clusterin/creatinine (r = 0.33, p < 0.01), and urine cystatin C/creatinine (r = 0.33, p < 0.05) levels. In a group of patients with abnormally high creatinine levels, significantly higher levels of serum cystatin C (p < 0.0001) and pFL-OPN (p < 0.001) were observed. Our results demonstrate that pFL-OPN reflect kidney injury among patients with leptospirosis.

Blood Levels of Galectin-9, an Immuno-Regulating Molecule, Reflect the Severity for the Acute and Chronic Infectious Diseases

“…In our previous study, a receiver operating characteristic (ROC) curve analysis revealed that plasma levels of Gal-9 had the greatest ability to discriminate patients with leptospirosis from healthy control subjects as compared with other markers (AUC: 0.899) ( Table 1 ) [ 63 ]. This finding may indicate that the plasma levels of Gal-9 could reflect the severity of leptospirosis, as they have been reported to do for dengue, malaria, and HIV/OI, given that cytokinemia is also frequently seen in this disease.…”

Both Full-Length and Protease-Cleaved Products of Osteopontin Are Elevated in Infectious Diseases

“…These findings indicate the involvement of OPN in kidney injury. A significant increase in urine NAG/Cr (p < 0.05) levels in leptospirosis patients has been described previously, and an increased urine NAG level is a highly specific marker of proximal tubular disease [111]. OPN may be involved in tubular dysfunction and is released by infiltrating inflammatory macrophages in tubules [145].…”

“…The mechanisms underlying the involvement of OPN cleavage in a cytokine storm are not clear; however, these findings further suggest that the cleaved forms of OPN can be used to monitor the severity of pathological inflammation and the therapeutic effects of tocilizumab in CP patients. [9,111,115]. ****; p < 0.0001, ***; p < 0.001, **; p < 0.01, *; p < 0.05.…”

“…We explored whether the OPN levels could be different between dengue, leptospirosis, and COVID-19 (Figure 5). The levels of FL-OPN showed a wide range in DF (1833 ± 159 ng/mL), DHF (1792 ± 193 ng/mL) [11], leptospirosis (443 ± 47.3 ng/mL) [111], and CP (455 ± 67.0 ng/mL). There were significant differences between DF and CV (p < 0.0001) or DF and CP (p = 0.0059), and between DHF and CV (p < 0.0001) or DHF and CP (p = 0.011).…”

“…(A) (B) The abbreviations are DF, dengue fever; DHF, dengue hemorrhagic fever. Data are from references [9] and [111,115]. ****; p < 0.0001, ***; p < 0.001, **; p < 0.01, *; p < 0.05.…”