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

Authors

  • Mehdi Azizmohammad Looha 1. Department of Biostatistics, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  • Fatemeh Masaebi 1. Department of Biostatistics, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  • 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

DOI:

https://doi.org/10.31661/gmj.v9i.1698

Keywords:

Chronic Kidney Diseases; Neutrophil Gelatinase-Associated Lipocalin; Cystatin C; Bayesian Approach; Latent Class Model; Sensitivity; Specificity

Abstract

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] 

References

Anjum M, Moorani KN, Sameen I, Mustufa MA, Kulsoom SJPjoms. Functional and structural abnormalities of the kidney and urinary tract in severely malnourished children-A hospital based study. Pak J Med Sci. 2016 Sep;32(5):1135. https://doi.org/10.12669/pjms.325.10457 Zhang G, Saito R, Sharma KJKi. A metabolite-GWAS (mGWAS) approach to unveil chronic kidney disease progression. Kidney Int. 2017 Jun 1;91(6):1274-6. https://doi.org/10.1016/j.kint.2017.03.022PMid:28501300 PMCid:PMC5989707 Dhondup T, Qian QJBp. Electrolyte and acid-base disorders in chronic kidney disease and end-stage kidney failure. Blood Purif. 2017;43(1-3):179-88. https://doi.org/10.1159/000452725PMid:28114143 Perico N, Remuzzi GJNDT. Chronic kidney disease: a research and public health priority. Nephrol Dial Transplant. 2012 Jul 3;27(suppl_3):iii19-26. https://doi.org/10.1093/ndt/gfs284PMid:22764188 Jager KJ, Fraser SDJNDT. The ascending rank of chronic kidney disease in the global burden of disease study. Nephrol Dial Transplant. 2017 Apr 1;32(suppl_2):ii121-8. https://doi.org/10.1093/ndt/gfw330PMid:28201666 Abadie V, Jabri BJIr. IL-15: a central regulator of celiac disease immunopathology. Immunol Rev. 2014 Jul;260(1):221-34. https://doi.org/10.1111/imr.12191PMid:24942692 PMCid:PMC4066219 Santos J, Martins LSJWjon. Estimating glomerular filtration rate in kidney transplantation: still searching for the best marker. World J Nephrol. 2015 Jul 6;4(3):345. https://doi.org/10.5527/wjn.v4.i3.345PMid:26167457 PMCid:PMC4491924 Tassone F, Gianotti L, Baffoni C, Pellegrino M, Castellano E, Borretta GJEP. KDIGO categories of glomerular filtration rate and parathyroid hormone secretion in primary hyperparathyroidism. Endocr Pract. 2015 Feb 25;21(6):629-33. https://doi.org/10.4158/EP14537.ORPMid:25716636 Levey AS, Becker C, Inker LAJJ. Glomerular filtration rate and albuminuria for detection and staging of acute and chronic kidney disease in adults: a systematic review. JAMA.2015 Feb 24;313(8):837-46. https://doi.org/10.1001/jama.2015.0602PMid:25710660 PMCid:PMC4410363 Levey AS, Inker LAJAJoKD. GFR as the "gold standard": estimated, measured, and true. Am J Kidney Dis. 2016 Jan 1;67(1):9-12. https://doi.org/10.1053/j.ajkd.2015.09.014PMid:26708193 Rule AD, Kremers WK. What is the correct approach for comparing GFR by different methods across levels of GFR?. CJASN. 2016 Sep 7; 11(9): 1518-1521. https://doi.org/10.2215/CJN.07530716PMid:27489300 PMCid:PMC5012480 Carrara F, Gaspari FJJoL, Medicine P. GFR measured by iohexol: the best choice from a laboratory perspective. jlpm. 2018 Sep 26;3. https://doi.org/10.21037/jlpm.2018.09.07 Zabell JR, Larson G, Koffel J, Li D, Anderson JK, Weight CJJJoe. Use of the Modification of Diet in Renal Disease Equation for Estimating Glomerular Filtration Rate in the Urologic Literature. J Endourol. 2016 Aug 1;30(8):930-3. https://doi.org/10.1089/end.2016.0143PMid:27150489 Beben T, Rifkin DEJAickd. GFR estimating equations and liver disease. . Adv Chronic Kidney Dis. 2015 Sep 1;22(5):337-42. https://doi.org/10.1053/j.ackd.2015.05.003PMid:26311594 PMCid:PMC4552961 Kumar BV, Mohan T. Retrospective comparison of estimated GFR using 2006 MDRD, 2009 CKD-EPI and Cockcroft-Gault with 24 hour urine creatinine clearance. J Clin Diagn Res. 2017 May;11(5):BC09. https://doi.org/10.7860/JCDR/2017/25124.9889PMid:28658750 PMCid:PMC5483652 Kuan Y, Hossain M, Surman J, El Nahas AM, Haylor JJNDT. GFR prediction using the MDRD and Cockcroft and Gault equations in patients with end-stage renal disease. Nephrol Dial Transplant.2005 Aug 23;20(11):2394-401. https://doi.org/10.1093/ndt/gfi076PMid:16115853 Botev R, Mallié J-P, Wetzels JF, Couchoud C, Schück OJCJotASoN. The clinician and estimation of glomerular filtration rate by creatinine-based formulas: current limitations and quo vadis. Clin J Am Soc Nephrol. 2011 Apr 1;6(4):937-50. https://doi.org/10.2215/CJN.09241010PMid:21454722 Husain SA, Willey JZ, Moon YP, Elkind MS, Sacco RL, Wolf M, et al. Creatinine-versus cystatin C-based renal function assessment in the Northern Manhattan Study. PLoS One. 2018 Nov 14;13(11):e0206839. https://doi.org/10.1371/journal.pone.0206839PMid:30427947 PMCid:PMC6235352 Wong CW, Teo BW, Lamoureux E, Ikram MK, Wang JJ, Tai ES, et al. Serum cystatin C, markers of chronic kidney disease, and retinopathy in persons with diabetes. J Diabetes Res. 2015;2015. https://doi.org/10.1155/2015/404280PMid:26576434 PMCid:PMC4630396 Chakraborty S, Kaur S, Tong Z, Batra SK, Guha S. Neutrophil gelatinase associated lipocalin: structure, function and role in human pathogenesis. InTech; 2011 Oct 5. https://doi.org/10.5772/18755 Shang W, Wang ZJCP, Science P. The Update of NGAL in Acute Kidney Injury. Curr Protein Pept Sci. 2017 Dec 1;18(12):1211-7. https://doi.org/10.2174/1389203717666160909125004PMid:27634444 Bakal U, Saraç M, Ciftci H, Tartar T, Kocdemir E, Aydin S, et al. Neutrophil gelatinase-associated lipocal in protein levels as an acute appendicitis biomarker in children. Springerplus. 2016 Dec 1;5(1):193 https://doi.org/10.1186/s40064-016-1853-xPMid:27026889 PMCid:PMC4769236 Rysz J, Gluba-Brzózka A, Franczyk B, Jabłonowski Z, Ciałkowska-Rysz AJIjoms. Novel biomarkers in the diagnosis of chronic kidney disease and the prediction of its outcome. Int J Mol Sci. 2017 Aug;18(8):1702. https://doi.org/10.3390/ijms18081702PMid:28777303 PMCid:PMC5578092 Fassett RG, Venuthurupalli SK, Gobe GC, Coombes JS, Cooper MA, Hoy WEJKi. Biomarkers in chronic kidney disease: a review. Kidney Int. 2011 Oct 2;80(8):806-21. https://doi.org/10.1038/ki.2011.198PMid:21697815 Gharishvandi F, Kazerouni F, Ghanei E, Rahimipour A, Nasiri MJIbj. Comparative assessment of neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C as early biomarkers for early detection of renal failure in patients with hypertension. Iran Biomed J. 2015 Apr;19(2):76. Szewczyk M, Wielkoszyński T, Zakliczyński M, Zembala M, editors. Plasma neutrophil gelatinase-associated lipocalin (NGAL) correlations with cystatin C, serum creatinine, and glomerular filtration rate in patients after heart and lung transplantation. Transplant Proc. 2009 Oct 1 (Vol. 41, No. 8, pp. 3242-3243). Elsevier. https://doi.org/10.1016/j.transproceed.2009.08.018PMid:19857721 Fassett RG, Robertson IK, Ball MJ, Geraghty DP, Cardinal JW, Coombes JSJNDT. Effects of atorvastatin on NGAL and cystatin C in chronic kidney disease: a post hoc analysis of the LORD trial. Nephrol Dial Transplant. 2011 May 4;27(1):182-9 https://doi.org/10.1093/ndt/gfr193PMid:21543653 Van Smeden M, Naaktgeboren CA, Reitsma JB, Moons KG, de Groot JAJAjoe. Latent class models in diagnostic studies when there is no reference standard-a systematic review. Am J Epidemiol.. 2013 Nov 21;179(4):423-31. https://doi.org/10.1093/aje/kwt286PMid:24272278 Hill NR, Fatoba ST, Oke JL, Hirst JA, O'Callaghan CA, Lasserson DS, et al. Global prevalence of chronic kidney disease-a systematic review and meta-analysis. PLoS One.. 2016 Jul 6;11(7):e0158765. https://doi.org/10.1371/journal.pone.0158765PMid:27383068 PMCid:PMC4934905 Yilmaz H, Kaya M, Çelik HT, Aylı MD, Canbakan BJIJoMMS. Correlation between Cystatin C and Creatinine Clearance among Primary Glomerulonephritis Patients with Stage 1-4 Chronic Renal Failure. IJMMS. 2013 Sep 23;1(2):22-6. Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, et al. Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet. 2005 Apr 2;365(9466):1231-8. https://doi.org/10.1016/S0140-6736(05)74811-X Malhotra R, Siew EDJCJotASoN. Biomarkers for the early detection and prognosis of acute kidney injury. Clin J Am Soc Nephrol. 2017 Jan 6;12(1):149-73. https://doi.org/10.2215/CJN.01300216PMid:27827308 PMCid:PMC5220647 Mitsnefes MM, Kathman TS, Mishra J, Kartal J, Khoury PR, Nickolas TL, et al. Serum neutrophil gelatinase-associated lipocalin as a marker of renal function in children with chronic kidney disease. Pediatr Nephrol. 2007 Jan 1;22(1):101. https://doi.org/10.1007/s00467-006-0244-xPMid:17072653 Basturk T, Sari O, Koc Y, Eren N, Isleem M, Kara E, et al. Prognostic significance of NGAL in early stage chronic kidney disease. Minerva Urol Nefrol.2017 Jun;69(3):307-12. https://doi.org/10.23736/S0393-2249.16.02770-3PMid:27768023 Bolignano D, Lacquaniti A, Coppolino G, Donato V, Campo S, Fazio MR, et al. Neutrophil gelatinase-associated lipocalin (NGAL) and progression of chronic kidney disease. Clin J Am Soc Nephrol. 2009 Feb 1;4(2):337-44. https://doi.org/10.2215/CJN.03530708PMid:19176795 PMCid:PMC2637601

Published

2020-06-22

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Section

Original Article