title: Neutrophil Gelatinase--Associated Lipocalin and Cystatin C Are Sensitive Markers of Renal Injury in Patients With Multiple Myeloma.
abstract: BACKGROUND
  Renal impairment is a common complication of patients with multiple myeloma (MM). We aimed to evaluate the clinical significance of 2 newly discovered biomarkers of renal injury, cystatin C (CysC), a protein reflecting glomerular filtration rate, and neutrophil gelatinase-associated lipocalin (NGAL), a protein reflecting tubular injuries.
  
  
  METHODS
  We studied 64 patients with newly diagnosed myeloma: 16 with asymptomatic (smoldering) MM and 48 with symptomatic myeloma; 8 patients with monoclonal gammopathy of undetermined significance (MGUS); and 20 healthy control subjects. Along with common blood and urine chemistry determinations, measurements of CysC, NGAL, β2-microglobulin, high-sensitivity C-reactive protein, and interleukin 6 were performed.
  
  
  RESULTS
  We found that only patients with symptomatic MM had increased levels of CysC compared to controls (P < .01); that serum NGAL levels were elevated in all patients compared to controls P < .001; that NGAL strongly correlated with both estimation of glomerular filtration rate (eGFR) (CysC) and eGFR (Modification of Diet in Renal Disease [MDRD] formula) (r = 0.616, P < .0001; and r = -0.371, P < .01, respectively); that CysC showed strong correlation with eGFR (r = -0.782, P < .001) and with the International Scoring System (ISS) (more pronounced in patients with ISS-3); and that receiver operating characteristic curve analysis showed that NGAL values of > 50.5 μg/L have a 80.8% sensitivity and 86.4% specificity for eGFR < 60 mL/min (area under the curve = 0.764).
  
  
  CONCLUSIONS
  These findings suggest that both NGAL and CysC are very sensitive markers that reflect renal impairment in newly diagnosed patients with MM. The high levels of NGAL in asymptomatic patients and in MGUS patients support the hypothesis of the presence of renal damage in these patients early in the course of their disease and may reveal NGAL to be an early marker that predicts the presence of renal impairment in MM.
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Medical School, Alexandra General Hospital, Athens, Greece.
authors.forename: Gerasimos-Petros
authors.initials: GP
authors.lastname: Papassotiriou
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Medical School, Alexandra General Hospital, Athens, Greece.
authors.forename: Efstathios
authors.initials: E
authors.lastname: Kastritis
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Medical School, Alexandra General Hospital, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Gkotzamanidou
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Medical School, Alexandra General Hospital, Athens, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Christoulas
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Medical School, Alexandra General Hospital, Athens, Greece.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Eleutherakis-Papaiakovou
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Medical School, Alexandra General Hospital, Athens, Greece.
authors.forename: Magdalini
authors.initials: M
authors.lastname: Migkou
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Medical School, Alexandra General Hospital, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Gavriatopoulou
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Medical School, Alexandra General Hospital, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Roussou
authors.affiliation: Department of Clinical Biochemistry, "Aghia Sophia" Children's Hospital, Athens, Greece.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Margeli
authors.affiliation: Department of Clinical Biochemistry, "Aghia Sophia" Children's Hospital, Athens, Greece. Electronic address: biochem@paidon-agiasofia.gr.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Papassotiriou
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Medical School, Alexandra General Hospital, Athens, Greece.
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
authors.affiliation: Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Medical School, Alexandra General Hospital, Athens, Greece.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Terpos
mesh_terms: D000209:Acute-Phase Proteins / Q000652:urine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood / Q000652:urine; D055316:Cystatin C / Q000097:blood* / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood* / Q000652:urine; D008297:Male; D008875:Middle Aged; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000097:blood / Q000652:urine; D009101:Multiple Myeloma / Q000097:blood / Q000150:complications* / Q000652:urine; D011518:Proto-Oncogene Proteins / Q000097:blood* / Q000652:urine; D012372:ROC Curve; D051437:Renal Insufficiency / Q000097:blood* / Q000209:etiology; D012680:Sensitivity and Specificity
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins
keywords: Acute renal injury; Bence Jones protein; Cystatin C; Myeloma nephropathy; NGAL