Evaluation of Neutrophil Gelatinase-Associated Lipocalin and Cystatin C in Early Diagnosis of Chronic Kidney Disease in the Absence of the Gold Standard

  • Fatemeh Masaebi 1. Department of Biostatistics, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran http://orcid.org/0000-0002-2227-8949
  • Mehdi Azizmohammad Looha 1. Department of Biostatistics, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran http://orcid.org/0000-0002-0700-1431
  • Zhuoyu Wang 2. Zhuoyu Wang, Academy of Medical Engineering and Translational Medicine, Tianjin University
  • Elaheh Zarean 3. Modeling in Health Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran
  • Maliheh Nasiri 4. Faculty of Nursing and Midwifery, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  • Faranak Kazerouni 5. Department of Laboratory Medicine, School of Allied Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  • Fatemeh Gharishvandi 6. Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  • Farid Zayeri 7. Proteomics Research Center and Department of Biostatistics, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Keywords: Chronic Kidney Diseases; Neutrophil Gelatinase-Associated Lipocalin; Cystatin C; Bayesian Approach; Latent Class Model; Sensitivity; Specificity


Background: Glomerular filtration rate (GFR) is considered as a gold standard of kidney function. However, using GFR as the gold standard is not common in clinical practice, because its direct measurement is usually expensive, cumbersome, and invasive. In the present study, we assessed the predictive power of two other biomarkers, Cystatin-C (Cys-C) and Neutrophil Gelatinase-Associated Lipocalin (NGAL) for early detection of chronic kidney diseases (CKD) in the absence of a gold standard. Materials and Methods: In this study, 72 patients who referred to the Shohadaye Tajrish Hospital of Tehran, Iran, for measuring their kidney function were studied. The ELISA method was utilized for measuring plasma NGAL (PNGAL) and serum Cys-C (SCys-C). The Bayesian latent class modeling approach was applied to asses the predictive power of these biomarkers. Results: While both the biomarkers had rather high sensitivities (PNGAL=91%, SCys-C= 89%), the specificity of SCys-C biomarker was very lower than the one of PNGAL (SCys-C=56%, PNGAL=94%). The estimated area under the receiver operating characteristic (ROC) curve for SCys-C as the single biomarker for the diagnosis of CKD was about 0.76, while a similar estimate for PNGAL was 0.93. The added value of PNGAL to SCys-C for the diagnosis of CKD in terms of the ROC curve was about 0.19, while the added value of SCys-C to PNGAL was less than 0.02. Conclusion: In general, our findings suggest that PNGAL can be utilized as a single reliable biomarker for early detection of CKD. In addition, results showed that when a perfect gold standard is not available, Bayesian approaches to latent class models could lead to more precise sensitivity and specificity estimates of imperfect tests. [GMJ.2020;9:e1698] 


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How to Cite
Masaebi, F., Azizmohammad Looha, M., Wang, Z., Zarean, E., Nasiri, M., Kazerouni, F., Gharishvandi, F., & Zayeri, F. (2020). Evaluation of Neutrophil Gelatinase-Associated Lipocalin and Cystatin C in Early Diagnosis of Chronic Kidney Disease in the Absence of the Gold Standard. Galen Medical Journal, 9, e1698. https://doi.org/10.31661/gmj.v9i0.1698
Original Article