NGAL distinguishes steroid sensitivity in idiopathic nephrotic syndrome

Abstract

Background: Idiopathic nephrotic syndrome (NS) is the most common glomerular disorder of childhood. Invasive biopsy remains the diagnostic method of choice for NS. Prognosis correlates with steroid responsiveness, from sensitive (SSNS) to resistant (SRNS). Neutrophil gelatinase-associated lipocalin (NGAL) has been demonstrated to be a powerful risk marker of chronic kidney disease progression. We set out to determine if urine NGAL can distinguish between patients with SRNS, SSNS, and healthy controls.

Methods: Urine and clinical data were collected from patients at Cincinnati Children's Hospital who were recently diagnosed with active nephrotic syndrome as well as healthy controls. Participants included SRNS (n = 15), SSNS (n = 14), and healthy controls (n = 10). Urinary NGAL was measured by ELISA and normalized to creatinine.

Results: Median NGAL was significantly (p < 0.001) higher in SRNS (172.3 ng/ml, IQR 18.8-789) than both SSNS (6.3 ng/ml, IQR 4.9-9.9) and healthy controls (6.5 ng/ml, IQR 4.2-9.1). The area under the curve (AUC) for NGAL to distinguish SRNS from SSNS was 0.91 (p < 0.0001). NGAL levels demonstrated a significant negative correlation with glomerular filtration rate (r = -0.5, p < 0.001). Results did not change with NGAL corrected for urine creatinine and were independent of the degree of proteinuria.

Conclusions: NGAL levels differentiate SSNS from SRNS and correlate with disease severity in SRNS.

Fig. 1

Urine NGAL measurements. Median urine NGAL was significantly higher in SRNS than both SSNS and healthy controls (p<0.001). Vertical dot plot overlays represent individual patient urine NGAL levels. NGAL neutrophil gelatinase-associated lipocalin; SRNS steroid resistant nephrotic syndrome; SSNS steroid sensitive nephrotic syndrome

Fig. 2

The NGAL/creatinine ratio has a high power to distinguish SRNS from SSNS. ROC analysis revealed an AUC of 0.91 (p<0.0001) for the detection of SRNS. The optimal cut-off value was 15 ng/mg NGAL/Cr with a sensitivity and specificity of 0.88. NGAL neutrophil gelatinase-associated lipocalin; SRNS steroid resistant nephrotic syndrome; SSNS steroid sensitive nephrotic syndrome; RDC receiver opening characteristic

Fig. 3

Urine neutrophil gelatinase-associated lipocalin (NGAL) correlate with disease severity. Median NGAL shows a significant negative correlation with estimated glomerular filtration rate (eGFR) (r=−0.5, p<0.01), indicating NGAL rises as renal function declines in all nephrotic syndrome (NS) patients