Early Urinary Biomarkers in Pediatric Autosomal Dominant Polycystic Kidney Disease (ADPKD): No Evidence in the Interest of Urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL)

Abstract

Background: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is increasingly diagnosed during childhood by the presence of renal cysts in patients with a positive familial history. No curative treatment is available and early detection and diagnosis confronts pediatricians with the lack of early markers to decide whether to introduce renal-protective agents and prevent the progression of renal failure. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is a tubular protein that has been recently proposed as an early biomarker of renal impairment in the ADPKD adult population. Methods: Urinary NGAL (uNGAL) levels were measured in 15 ADPKD children and compared with 15 age and gender matched controls using parametric, non-parametric, and Bayesian statistics. We also tested the association of uNGAL levels with markers of disease progression, such as proteinuria, albuminuria, blood pressure, and Total Kidney Volume (TKV) using correlation analysis. TKV was calculated by ultrasound, using the ellipsoid method. Results: No difference in mean uNGAL levels was observed between groups (ADPKD: 26.36 ng/ml; Controls: 27.24 ng/ml; P = 0.96). Moreover, no correlation was found between uNGAL and proteinuria ( P = 0.51), albuminuria ( P = 0.69), TKV ( P = 0.68), or mean arterial pressure ( P = 0.90). By contrast, TKV was positively correlated with proteinuria ( P = 0.04), albuminuria ( P = 0.001), and mean arterial pressure ( P = 0.03). Conclusion: uNGAL did not confirm its superiority as a marker of disease progression in a pediatric ADPKD population. In the contrary, TKV appears to be an easy measurable variable and may be promising as a surrogate marker to follow ADPKD progression in children.

The Review of Current Knowledge on Neutrophil Gelatinase-Associated Lipocalin (NGAL)

“…Thus, NGAL has been suggested to be involved in the cyst growth process in ADPKD [ 130 ]. However, its role in ADPKD is not clear [ 133 ]. Some reports have shown that NGAL is able to inhibit cyst enlargement [ 134 ].…”

Secreted Neutrophil Gelatinase-Associated Lipocalin Shows Stronger Ability to Inhibit Cyst Enlargement of ADPKD Cells Compared with Nonsecreted Form

“…Neutrophil gelatinase-associated lipocalin (NGAL), a 22-kD secreted protein, is regarded as a biomarker for kidney injuries, including PKD in adults [19] (but not in children [20]), chronic kidney disease [21] and acute kidney ischemia [22]. The mechanism of NGAL protein increasing in patient urine is not clear, it has been proposed that accumulated NGAL in urine relates to deciliation of the renal epithelial cells as a result of injury [23].…”