Neutrophil Gelatinase-Associated Lipocalin in Patients with Autosomal-Dominant Polycystic Kidney Disease

Abstract

It is known that many tubular proteins are involved in the pathogenesis of autosomal-dominant polycystic kidney disease (ADPKD), which causes 8–10% of the cases of end-stage renal disease (ESRD) worldwide. Neutrophil gelatinase-associated lipocalin (NGAL) is a protein expressed on tubular cells of which the production is markedly increased in response to harmful stimuli such as ischemia or toxicity. In the present study, serum and urinary NGAL levels were evaluated in 26 ADPKD subjects. Both levels were significantly higher in patients than in controls (sNGAL 174 ± 52 vs. 50 ± 27 ng/ml, p < 0.05; uNGAL 119 ± 42 vs. 7 ± 6 ng/ml, p < 0.005) and a close correlation was also found between these parameters and the residual renal function (sNGAL/GFR: r = –0.8, p = 0.006; sNGAL/Creatinine: r = 0.9, p = 0.007; uNGAL/GFR: r = –0.49, p < 0.05; uNGAL/Creatinine: r = 0.84, p < 0.001). Patients were further divided into two groups according to the cystic development assessed with echotomography; subjects with higher cystic growth (HCG) presented higher sNGAL and uNGAL levels with respect to others (sNGAL: 242 ± 89 vs. 88 ± 34 ng/ml, p < 0.05; uNGAL: 158 ± 45 vs. 73 ± 27 ng/ml, p < 0.05). The strict correlation between NGAL levels and residual renal function is perfectly in accord with recent studies on patients with other ESRD-associated diseases. We can hypothesize that tubular cells produce big quantities of NGAL as a consequence of increased apoptosis following chronic damage or as a compensatory response, similar to that observed in acute stress conditions (ischemia, toxicity ...). Finally, our last finding that patients with HCG showed higher levels of NGAL suggests that this protein could be also involved in the cyst growth process, as previously reported about epithelial and tumoral expansion.

Serum Neutrophil Gelatinase-Associated Lipocalin as a Marker of Renal Function in Non-Diabetic Patients with Stage 2–4 Chronic Kidney Disease

“…Moreover, Ding et al [12] demonstrated the upregulation of tubular expression of NGAL in biopsies from Lee grade III IgA nephropathy patients as well as increased urinary excretion of NGAL in these subjects (even in Lee grade II). In addition, the strict correlation between NGAL levels and residual renal function were reported in 26 APKD patients by Bolignano et al [13] In our study, we confirmed a recent finding by Mitsnefes et al, [5] who showed that NGAL could represent a marker of renal function in children with chronic kidney disease. They also found out that eGFR calculated using the Schwartz formula correlated very significantly with both cystatin C and NGAL.…”

Urinary NGAL Marks Cystic Disease in HIV-Associated Nephropathy

“…In HIVAN, we identified this source as cystic tubular epithelia. This finding is consistent with the observation that uNGAL is expressed in patients with poly- cystic kidney disease, 21 especially in those with rapid cyst enlargement. We first identified NGAL as a tubulogenic factor, 22 a property supported by studies in cell lines.…”

Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Progression of Chronic Kidney Disease

“…Interestingly, apart from the already cited predictive value, a strict, independent, and inverse correlation with estimated GFR was described for both sNGAL and uNGAL, suggesting that under these particular conditions this protein may also represent a surrogate index of residual renal function, similar to what has previously been described elsewhere (27)(28)(29).…”