title: [Genotype-phenotype correlation in ADPKD: a possible role for NGAL?].
abstract: BACKGROUND
  Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of chronic kidney disease (CKD) in adults. It is associated with both inter- and intra- familial variability, which can be explained by genetic heterogeneity, modifier genes and a genetic background. NGAL, a 25-kDa protein released from tubular cells after harmful stimuli, is a new biomarker. Recent studies suggest a possible role for NGAL in CKD. The aim of this study was to investigate NGAL in the context of genotype-phenotype correlation in ADPKD.
  
  
  METHODS
  We measured plasma NGAL, creatinine (Cr), and urea in 18 ADPKD patients on dialysis (PKD1_TRS), 29 of their relatives with CKD stage II-III (PKD1_AMB), 33 wild-type relatives (PKD1_WT), 12 subjects in CKD stage II-III with confirmed mutation in PKD2 and 30 healthy controls (CTR). Cr, urea and CysC were measured according to standard methods. Plasma NGAL was measured using point-of-care test. Estimated glomerular filtration rate (eGFR) was calculated with a 4-variable standardized-MDRD formula.
  
  
  RESULTS
  Plasma NGAL, CysC, Cr and urea levels in PKD1_TRS were significantly higher than CTR (all with p<0,001). PKD1_TRS pts had significantly higher NGAL, CysC, Cr and Urea levels compared to PKD1_AMB and PKD1_WT. PKD1_AMB pts had higher NGAL, CysC, Urea and Cr levels compared to PKD1_WT relatives. NGAL CysC, Cr and urea values were similar between PKD1_WT and CTR (p>0.05). NGAL levels were not significantly different in ADPKD patients in CKD stage II-III with mutation in PKD1 or PKD2 (86 pg/mL, IQR 60-109 vs 82 pg/mL,IQR 63-169). NGAL correlated well (all with p<0.001) with CysC (r=0.95), Cr (r=0.89), urea (r=0.76) and inversely with eGFR (r=-0.81). A strong correlation between CysC and residual renal function was observed (CysC/eGFR: r=-0.86; CysC/Cr: r=0.7; CysC/Urea: r=0.79, all with p<0.001).
  
  
  CONCLUSIONS
  This is the first study to evaluate plasma NGAL in the context of genotype-phenotype correlation. In ADPKD, NGAL levels were higher in patients already on Renal Replacement Therapy (RRT) compared to their affected relatives not on RRT. WT relatives had normal NGAL and CysC levels: these could be considered a better CTR group because they share the same genetic background with ADPKD subjects. No differences were found in NGAL levels between PKD1 and PKD2 patients in CKD stage II-III. Furthermore, the results indicate that NGAL correlates closely with renal function and CysC levels.
authors.forename: Grazia Maria
authors.initials: GM
authors.lastname: Virzì
authors.forename: Fiorella
authors.initials: F
authors.lastname: Gastaldon
authors.forename: Valentina
authors.initials: V
authors.lastname: Corradi
authors.forename: Massimo
authors.initials: M
authors.lastname: de Cal
authors.forename: Dinna N
authors.initials: DN
authors.lastname: Cruz
authors.forename: Maurizio
authors.initials: M
authors.lastname: Clementi
authors.forename: Claudio
authors.initials: C
authors.lastname: Ronco
mesh_terms: D000209:Acute-Phase Proteins; D015415:Biomarkers / Q000097:blood; D005260:Female; D005838:Genotype; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016891:Polycystic Kidney, Autosomal Dominant / Q000097:blood* / Q000150:complications / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000097:blood*; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications / Q000235:genetics
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins