Neutrophil gelatinase-associated lipocalin in patients with autosomal-dominant polycystic kidney disease

Am J Nephrol. 2007;27(4):373-8. doi: 10.1159/000103912. Epub 2007 Jun 13.

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.

MeSH terms

  • Acute-Phase Proteins / urine*
  • Adult
  • Case-Control Studies
  • Cysts / physiopathology
  • Female
  • Humans
  • Kidney Function Tests
  • Kidney Tubules / metabolism*
  • Kidney Tubules / physiopathology
  • Lipocalin-2
  • Lipocalins
  • Male
  • Middle Aged
  • Polycystic Kidney, Autosomal Dominant / blood*
  • Polycystic Kidney, Autosomal Dominant / physiopathology
  • Polycystic Kidney, Autosomal Dominant / urine*
  • Proto-Oncogene Proteins / blood*
  • Proto-Oncogene Proteins / urine*

Substances

  • Acute-Phase Proteins
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Proto-Oncogene Proteins