Ukr.Biochem.J. 2021; Volume 93, Issue 6, Nov-Dec, pp. 55-63
doi: https://doi.org/10.15407/ubj93.06.055
Urine neutrophil gelatinase-associated lipocalin as an early biochemical marker of microalbuminuria in predicting early kidney damage in patients with type 2 diabetes mellitus
P. J. Padmini, V. Ashok*
Shri Sathya Sai Medical College and Research Institute, Sri Balaji Vidyapeeth Deemed to be University, Tamilnadu, India;
*e-mail: dr.ashokmbbs1986@gmail.com
Received: 08 July 2021; Accepted: 12 November 2021
Diabetic nephropathy is one of the microvascular complications of diabetes mellitus. The study was done to evaluate the diagnostic value of neutrophil gelatinase-associated lipocalin (NGAL) urine level as a biomarker for the early detection of nephropathy in type 2 diabetic patients. This study was performed on 150 patients with type 2 diabetes mellitus classified into three equal groups according to their urine albumin/creatinine ratio (ACR), including patients with normoalbuminuria (ACR < 30 mg/g creatinine), microalbuminuria (ACR = 30–300 mg/g creatinine) and macroalbuminuria (ACR > 300 mg/g creatinine). Fifty apparently healthy subjects were selected as a control group. Urine NGAL was estimated by a particle-enhanced turbidimetric immunoassay using Hitachi 917 analyzer. The serum level of glucose and creatinine was also estimated. The results showed that NGAL urine level was significantly elevated in diabetes patient groups with microalbuminuria and macroalbuminuria when compared to the control group and diabetes patient group with normoalbuminuria. The levels of urine NGAL correlated positively with microalbuminuria in patients with diabetes. Receiver operating characteristic curves revealed that urine NGAL had a higher diagnostic value for diabetic nephropathy early detection compared to ACR and microalbuminuria in patients with diabetes mellitus.
Keywords: albumin/creatinine ratio microalbuminuria, diabetic nephropathy, gelatinase-associated lipocalin
References:
- Fowler MJ. Microvascular and Macrovascular Complications of Diabetes. Clin Diabet. 2008;26(2):77-82. CrossRef
- Stanton RC. Clinical challenges in diagnosis and management of diabetic kidney disease. Am J Kidney Dis. 2014;63(2 Suppl 2):S3-21. PubMed, CrossRef
- O’Hare AM, Bertenthal D, Covinsky KE, Landefeld CS, Sen S, Mehta K, Steinman MA, Borzecki A, Walter LC. Mortality risk stratification in chronic kidney disease: one size for all ages? J Am Soc Nephrol. 2006;17(3):846-853. PubMed, CrossRef
- Reutens AT. Epidemiology of diabetic kidney disease. Med Clin North Am. 2013;97(1):1-18. PubMed, CrossRef
- Bonventre JV. Can we target tubular damage to prevent renal function decline in diabetes? Semin Nephrol. 2012;32(5):452-462. PubMed, PubMedCentral, CrossRef
- De Carvalho JAM, Tatsch E, Hausen BS, Bollick YS, Moretto MB, Duarte T, Duarte MMMF, Londero SWK, Premaor MO, Comim FV, Delanghe JR, Moresco RN. Urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin as indicators of tubular damage in normoalbuminuric patients with type 2 diabetes. Clin Biochem. 2016;49(3):232-236. PubMed, CrossRef
- Prasannakumar M, Rajput R, Seshadri K, Talwalkar P, Agarwal P, Gokulnath G, Kotak B, Raza A, Vasnawala H, Teli C. An observational, cross-sectional study to assess the prevalence of chronic kidney disease in type 2 diabetes patients in India (START -India). Indian J Endocrinol Metab. 2015;19(4):520-523. PubMed, PubMedCentral, CrossRef
- MacIsaac RJ, Tsalamandris C, Panagiotopoulo S, Smith TJ, McNeil KJ, Jerums G. Nonalbuminuric renal insufficiency in type 2 diabetes. Diabetes Care. 2004;27(1):195-200. PubMed, CrossRef
- Phillips AO. The role of renal proximal tubular cells in diabetic nephropathy. Curr Diab Rep. 2003;3(6):491-496. PubMed, CrossRef
- Nauta FL, Boertien WE, Bakker SJL, van Goor H, van Oeveren W, de Jong PE, Bilo H, Gansevoort RT. Glomerular and tubular damage markers are elevated in patients with diabetes. Diabetes Care. 2011;34(4):975-981. PubMed, PubMedCentral, CrossRef
- Schmidt-Ott KM, Mori K, Li JY, Kalandadze A, Cohen DJ, Devarajan P, Barasch J. Dual action of neutrophil gelatinase-associated lipocalin. J Am Soc Nephrol. 2007;18(2):407-413. PubMed, CrossRef
- Baxmann AC, Ahmed MS, Marques NC, Menon VB, Pereir AB, Kirsztajn GM, Heilberg IP. Influence of muscle mass and physical activity on serum and urinary creatinine and serum cystatin C. Clin J Am Soc Nephrol. 2008;3(2):348-354. PubMed, PubMedCentral, CrossRef
- Han WK, Wagener G, Zhu Y, Wang S, Lee HT. Urinary biomarkers in the early detection of acute kidney injury after cardiac surgery. Clin J Am Soc Nephrol. 2009;4(5):873-882. PubMed, PubMedCentral, CrossRef
- Haase M, Bellomo R, Devarajan P, Schlattmann P, Haase-Fielitz A, NGAL Meta-analysis Investigator Group. Accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in diagnosis and prognosis in acute kidney injury: a systematic review and meta-analysis. Am J Kidney Dis. 2009;54(6):1012-1024. PubMed, CrossRef
- Paccaud F, Schlüter-Fasmeye V, Wietlisbach V, Bovet P. Dyslipidemia and abdominal obesity: an assessment in three general populations. J Clin Epidemiol. 2000;53(4):393-400. PubMed, CrossRef
- Beach EF, Turner JJ. An enzymatic method for glucose determination in body fluids. Clin Chem. 1958;4(6):462-475. PubMed
- Moss GA, Bondar RJ, Buzzelli DM. Kinetic enzymatic method for determining serum creatinine. Clin Chem. 1975;21(10):1422-1426. PubMed
- Bacci MR, Chehter EZ, Azzalis LA, Costa de Aguiar Alves B, Fonseca FLA. Serum NGAL and Cystatin C Comparison With Urinary Albumin-to-Creatinine Ratio and Inflammatory Biomarkers as Early Predictors of Renal Dysfunction in Patients With Type 2 Diabetes. Kidney Int Rep. 2016;2(2):152-158. PubMed, PubMedCentral, CrossRef
- Kaul A, Behera MR, Rai MK, Mishra P, Bhaduaria DS, Yadav S, Agarwal V, Karoli R, Prasad N, Gupta A, Sharma RK. Neutrophil Gelatinase-associated Lipocalin: As a Predictor of Early Diabetic Nephropathy in Type 2 Diabetes Mellitus. Indian J Nephrol. 2018;28(1):53-60. PubMed, PubMedCentral, CrossRef
- Yaqoob M, Patrick AW, McClelland P, Stevenson A, Mason H, White MC, Bell GM. Relationship between markers of endothelial dysfunction, oxidant injury and tubular damage in patients with insulin-dependent diabetes mellitus. Clin Sci (Lond). 1993;85(5):557-562. PubMed, CrossRef
- Ronco C. N-GAL: diagnosing AKI as soon as possible. Crit Care. 2007;11(6):173. PubMed, PubMedCentral, CrossRef
- Panee J. Monocyte Chemoattractant Protein 1 (MCP-1) in obesity and diabetes. Cytokine. 2012;60(1):1-12. PubMed, PubMedCentral, CrossRef
- Nielsen SE, Sugaya T, Hovind P, Baba T, Parving HH, Rossing P. Urinary liver-type fatty acid-binding protein predicts progression to nephropathy in type 1 diabetic patients. Diabetes Care. 2010;33(6):1320-1324. PubMed, PubMedCentral, CrossRef
- Nielsen SE, Schjoedt KJ, Astrup AS, Tarnow L, Lajer M, Hansen PR, Parving HH, Rossing P. Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Kidney Injury Molecule 1 (KIM1) in patients with diabetic nephropathy: a cross-sectional study and the effects of lisinopril. Diabet Med. 2010;27(10):1144-1150. PubMed, CrossRef
- Gazareen SS, Korani MAER, Tawfeek AR, Omar TA, Dwidar GIEA. Role of urinary neutrophil gelatinase-associated lipocalin in diabetic and nondiabetic patients with nephropathy. Menoufia Med J. 2021;34(1):135-140. CrossRef
- Quang TH, Nguyet MP, Thao DP, Thi MH, Phuong Thi Dam L, Thi HH, Van AP, Luong TC, Tuyet MNT, Duy QD, Nhu BD, Duc TN. Evaluation of Urinary Neutrophil Gelatinase Associated Lipocalin and Kidney Injury Molecule-1 as Diagnostic Markers for Early Nephropathy in Patients with Type 2 Diabetes Mellitus. Diabetes Metab Syndr Obes. 2020;13:2199-2207. PubMed, PubMedCentral, CrossRef
- Sun YM, Su Y, Li J, Wang LF. Recent advances in understanding the biochemical and molecular mechanism of diabetic nephropathy. Biochem Biophys Res Commun. 2013;433(4):359-361. PubMed, CrossRef
- Currie G, McKay G, Delles C. Biomarkers in diabetic nephropathy: Present and future. World J Diabetes. 2014;5(6):763-776. PubMed, PubMedCentral, CrossRef
- Kim SS, Song SH, Kim IJ, Yang JY, Lee JG, Kwak IS, Kim YK. Clinical implication of urinary tubular markers in the early stage of nephropathy with type 2 diabetic patients. Diabetes Res Clin Pract. 2012;97(2):251-257. PubMed, CrossRef
- Bolignano D, Lacquaniti A, Coppolino G, Donato V, Fazio MR, Nicocia G, Buemi M. Neutrophil gelatinase-associated lipocalin as an early biomarker of nephropathy in diabetic patients. Kidney Blood Press Res. 2009;32(2):91-98. PubMed, CrossRef
- Jiao LY, Guo Q, Song Z. Diagnostic value of urinary neutrophil gelatinase associated lipocalin and serum cystatin C on diabetic nephropathy. J Xinxiang Med Coll. 2011;(5):21.
- Lacquaniti A, Donato V, Pintaudi B, Di Vieste G, Chirico V, Buemi A, Di Benedetto A, Arena A, Buemi M. “Normoalbuminuric” diabetic nephropathy: tubular damage and NGAL. Acta Diabetol. 2013;50(6):935-942. PubMed, CrossRef
- Zachwieja J, Soltysiak J, Fichna P, Lipkowska K, Stankiewicz W, Skowronska B, Kroll P, Lewandowska-Stachowiak M. Normal-range albuminuria does not exclude nephropathy in diabetic children. Pediatr Nephrol. 2010;25(8):1445-1451. PubMed, CrossRef
- Assal HS, Tawfeek S, Rasheed EA, El-Lebedy D, Thabet EH. Serum cystatin C and tubular urinary enzymes as biomarkers of renal dysfunction in type 2 diabetes mellitus. Clin Med Insights Endocrinol Diabetes. 2013;6:7-13. PubMed, PubMedCentral, CrossRef
- Fathimah M, Alicezah MK, Thevarajah M. Neutrophil gelatinase‑associated lipocalin (NGAL): An early marker for diabetic nephropathy. Int J Diabetes Dev Ctries. 2012;32(1):19‑24. CrossRef
