Neutrophil gelatinase-associated lipocalin as a biomarker of nephropathy in sickle cell disease

Ann Hematol. 2021 Jun;100(6):1401-1409. doi: 10.1007/s00277-021-04500-4. Epub 2021 Apr 2.

Abstract

Sickle cell nephropathy (SCN) develops via altered hemodynamics and acute kidney injury, but conventional screening tests remain normal until advanced stages. Early diagnostic biomarkers are needed so that preventive measures can be taken. This study evaluates the role of neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker of SCN in steady state and vaso-occlusive crisis (VOC). In this case-control study, 74 sickle cell disease (SCD) patients (37 in steady state and 37 in VOC) and 53 control subjects had hematological and biochemical measurements including plasma and urine NGAL. Univariate and logistic regression analyses were used to find the associations between variables. The receiver operating characteristic (ROC) curve was used to determine the diagnostic performance characteristics of plasma and urine NGAL for detection of VOC. Plasma and urine NGAL, urine microalbumin:creatinine ratio, and urine protein:creatinine ratio were significantly higher in VOC. Microalbuminuria was present in 17.1% steady state and 32.0% VOC patients. Microalbuminuria showed significant correlations with age, plasma NGAL, WBC, and hemolytic parameters. Area under the ROC curve for plasma NGAL was 0.69 (95%CI = 0.567-0.813; p = 0.006) and 0.86 (95%CI = 0.756-0.954; p < 0.001) for urine NGAL. Urine NGAL cut-off value of 12.0 ng/mL had 95% sensitivity and 65% specificity. These results confirm the presence of nephropathy during VOC and suggest that plasma and urine NGAL would be useful in the identification of SCN. Urine NGAL should be used as the screening biomarker, and patients with VOC and urine NGAL > 12.0 ng/mL should be selected for aggressive management to prevent progression of renal damage.

Keywords: Glomerular filtration rate; Neutrophil gelatinase–associated lipocalin; Sickle cell disease; Sickle cell nephropathy; Urine microalbumin:creatinine ratio.

MeSH terms

  • Acute Kidney Injury / blood*
  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / urine
  • Adult
  • Anemia, Sickle Cell / blood*
  • Anemia, Sickle Cell / complications
  • Anemia, Sickle Cell / urine
  • Biomarkers / blood
  • Biomarkers / urine
  • Case-Control Studies
  • Female
  • Humans
  • Lipocalin-2 / blood*
  • Lipocalin-2 / urine
  • Male
  • ROC Curve

Substances

  • Biomarkers
  • LCN2 protein, human
  • Lipocalin-2

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