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

: 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-ß-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.

Urine Levels of Defensin α1 Reflect Kidney Injury in Leptospirosis Patients.

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-ß-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.

Combined antibody and DNA detection for early diagnosis of leptospirosis after a disaster.

Early diagnosis based on laboratory confirmation is essential for managing leptospirosis. This study investigated the effectiveness of a novel method of detecting leptospirosis that combines measurement of anti-Leptospira antibodies by the microscopic agglutination test (MAT), enzyme-linked immunosorbent assay (ELISA), and immunochromatographic test (ICT) and leptospiral DNA by loop-mediated isothermal amplification (LAMP) and real-time PCR in plasma and 2 types of urine pellets. Of 113 suspected cases, 68.1%, 76.1%, and 60.2% were positive by MAT, ELISA, and ICT, respectively. Real-time PCR using DNA purified from urine pellets collected by low-speed centrifugation yielded positive signals for patients in late acute as well as early phase who were positive by LAMP using plasma DNA or urine pellets. Among antibody-negative patients, 9.5% were positive by DNA detection. These findings indicate that the leptospirosis detection rate is increased by combining antibody and DNA detection, providing a new tool for timely diagnosis of infection.