Neutrophil Gelatinase Associated Lipocalin (NGAL) in Leptospirosis Acute Kidney Injury: A Multicenter Study in Thailand

Abstract

AKI is one of the most serious complications of leptospirosis, an important zoonosis in the tropics. Recently, NGAL, one of the novel AKI biomarkers, is extensively studied in various specific settings such as sepsis, cardiac surgery, and radiocontrast nephropathy. In this multicenter study, we aimed to study the role of NGAL as an early marker and an outcome predictor of leptospirosis associated AKI. Patients who presented with clinical suspiciousness of leptospirosis were prospectively enrolled in 9 centers from August 2012 to November 2014. The first day of enrollment was the first day of clinical suspicious leptospirosis. Blood and urine samples were serially collected on the first three days and day 7 after enrollment. We used three standard techniques (microscopic agglutination test, direct culture, and PCR technique) to confirm the diagnosis of leptospirosis. KDIGO criteria were used for AKI diagnosis. Recovery was defined as alive and not requiring dialysis during hospitalization or maintaining maximum KDIGO stage at hospital discharge. Of the 221 recruited cases, 113 cases were leptospirosis confirmed cases. Thirty seven percent developed AKI. Median uNGAL and pNGAL levels in those developing AKI were significantly higher than in patients not developing AKI [253.8 (631.4) vs 24.1 (49.6) ng/ml, p < 0.001] and [1,030 (802.5) vs 192.0 (209.0) ng/ml, p < 0.001], respectively. uNGAL and pNGAL levels associated with AKI had AUC-ROC of 0.91, and 0.92, respectively. Both of urine NGAL and pNGAL level between AKI-recovery group and AKI-non recovery were comparable. From this multicenter study, uNGAL and pNGAL provided the promising result to be a marker for leptospirosis associated AKI. However, both of them did not show the potential role to be the predictor of renal recovery in this specific setting.

A Dormant Microbial Component in the Development of Pre-Eclampsia1

“…However, it is not a specific biomarker for AKI vs sepsis [779; 782–790] and its origin in sepsis differs [791; 792]. Of course it can be the sepsis that leads to the AKI [793; 794]. Fairly obviously, while it does tend to be increased during PE, we again see its direct role as an antimicrobial and marker of sepsis as highly supportive of our present thesis.…”

Urine Levels of Defensin α1 Reflect Kidney Injury in Leptospirosis Patients

“…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].…”

“…Azithromycin and doxycycline have been reported to be effective in the treatment of this disease [9]. Azithromycin was also shown to inhibit neutrophil activation [10,11], and involvement of neutrophils and elevation of neutrophil-related activation markers such as neutrophil gelatinase-associated lipocalin (NGAL) have been reported in leptospirosis patients [12]. We recently demonstrated that urinary leptospiral DNA, some of which is presumably from phagocytized bacteria in leukocytes, increased the detection rate of leptospirosis [13].…”

A Dormant Microbial Component in the Development of Preeclampsia

“…However, it is not a specific biomarker for AKI vs. sepsis (839, 842–850) and its origin in sepsis differs (851, 852). Of course, it can be the sepsis that leads to the AKI (853, 854). Fairly obviously, while it does tend to be increased during PE, we again see its direct role as an antimicrobial and marker of sepsis as highly supportive of our present thesis.…”