Evaluation of Early Biomarkers of Renal Dysfunction in Diabetic Patients

Overview

Journal Saudi Med J

Specialty General Medicine

Date 2020 Jul 1

PMID 32601635

Citations 6

Authors

Shrouq F Al-Hazmi

Hoda G M Gad

Aliaa A Alamoudi

Basmah M Eldakhakhny

Sarah K Binmahfooz

Amani M Alhozali

Affiliations

Soon will be listed here.

Abstract

Objectives: To evaluate 2 renal tubular enzymes; urinary neutrophil gelatinase-associated lipocalin (uNGAL), and urinary N-acetyl-beta-D-glucosaminidase (uNAG), and serum Cystatin C as candidate biomarkers for early diagnosis of early stage of diabetic nephropathy (DB) in patients with type 2 diabetes mellitus (T2DM).

Methods: This cross-sectional study was carried out at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia during the period between May 2017 and May 2018 and was conducted on 86 patients with T2DM. Patients were classified according to their albumin/creatinine ratio (ACR) into 3 groups; a normal albuminuria group with ACR less than 30 mg/g creatinine, a moderately increased albuminuria group with ACR: 30-299 mg/g creatinine, and a severely increased albuminuria group with ACR ≥300 mg/g. Healthy adults were recruited as a control group. Urine uNGAL, uNAG, and serum Cystatin C were measured in all patients.

Results: Compared with healthy control, diabetic patients with normal albuminuria excreted significantly higher levels of uNGAL (p less than 0.001). In addition, significantly elevated uNGAL, uNAG and cystatin C levels were observed in moderately increased albuminuria and severely increased albuminuria groups when compared to the control and normoalbuminuric groups (p less than 0.001). urinary neutrophil gelatinase-associated lipocalin, urinary N-acetyl-beta-D-glucosaminidase and Cystatin C showed a positive correlation with fasting blood glucose (FBG), HbA1c, duration of diabetes, urea, creatinine, and ACR.

Conclusion: Our results indicated that uNGAL could be a sensitive biomarker for early renal dysfunction in diabetic patients while uNAG and serum Cystatin C might have prognostic value.

Citing Articles

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Early Detection of Diabetic Nephropathy Based on Urinary and Serum Biomarkers: An Updated Systematic Review.

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Increased serum cystatin C levels and responses of pancreatic α- and β-cells in type 2 diabetes.

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References

Malyszko J, Malyszko J, Bachorzewska-Gajewska H, Poniatowski B, Dobrzycki S, Mysliwiec M . Neutrophil gelatinase-associated lipocalin is a new and sensitive marker of kidney function in chronic kidney disease patients and renal allograft recipients. Transplant Proc. 2009; 41(1):158-61. DOI: 10.1016/j.transproceed.2008.10.088. View

Han W, Wagener G, Zhu Y, Wang S, Lee H . Urinary biomarkers in the early detection of acute kidney injury after cardiac surgery. Clin J Am Soc Nephrol. 2009; 4(5):873-82. PMC: 2676184. DOI: 10.2215/CJN.04810908. View

Hemdahl A, Gabrielsen A, Zhu C, Eriksson P, Hedin U, Kastrup J . Expression of neutrophil gelatinase-associated lipocalin in atherosclerosis and myocardial infarction. Arterioscler Thromb Vasc Biol. 2005; 26(1):136-42. DOI: 10.1161/01.ATV.0000193567.88685.f4. View

Kim S, Song S, Kim I, Yang J, Lee J, Kwak I . Clinical implication of urinary tubular markers in the early stage of nephropathy with type 2 diabetic patients. Diabetes Res Clin Pract. 2012; 97(2):251-7. DOI: 10.1016/j.diabres.2012.02.019. View

Nielsen S, Sugaya T, Tarnow L, Lajer M, Schjoedt K, Astrup A . Tubular and glomerular injury in diabetes and the impact of ACE inhibition. Diabetes Care. 2009; 32(9):1684-8. PMC: 2732168. DOI: 10.2337/dc09-0429. View

Assal H, Tawfeek S, Rasheed E, El-Lebedy D, Thabet E . 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. PMC: 3738377. DOI: 10.4137/CMED.S12633. View

Nauta F, Boertien W, Bakker S, Goor H, van Oeveren W, de Jong P . Glomerular and tubular damage markers are elevated in patients with diabetes. Diabetes Care. 2011; 34(4):975-81. PMC: 3064060. DOI: 10.2337/dc10-1545. View

Ambade V, Sing P, Somani B, Basanna D . Urinary N-acetyl beta glucosaminidase and gamma glutamyl transferase as early markers of diabetic nephropathy. Indian J Clin Biochem. 2012; 21(2):142-8. PMC: 3454003. DOI: 10.1007/BF02912930. View

Kaul A, Behera M, Rai M, Mishra P, Bhaduaria D, Yadav S . Neutrophil Gelatinase-associated Lipocalin: As a Predictor of Early Diabetic Nephropathy in Type 2 Diabetes Mellitus. Indian J Nephrol. 2018; 28(1):53-60. PMC: 5830810. DOI: 10.4103/ijn.IJN_96_17. View

10.

Wang C, Li C, Gong W, Lou T . New urinary biomarkers for diabetic kidney disease. Biomark Res. 2013; 1(1):9. PMC: 4177619. DOI: 10.1186/2050-7771-1-9. View

11.

Cowland J, Borregaard N . Molecular characterization and pattern of tissue expression of the gene for neutrophil gelatinase-associated lipocalin from humans. Genomics. 1997; 45(1):17-23. DOI: 10.1006/geno.1997.4896. View

12.

Kim S, Lee Y, Lee S, Kang E, Cha B, Kim J . Urinary N-acetyl-β-D-glucosaminidase, an early marker of diabetic kidney disease, might reflect glucose excursion in patients with type 2 diabetes. Medicine (Baltimore). 2016; 95(27):e4114. PMC: 5058844. DOI: 10.1097/MD.0000000000004114. View

13.

Decavele A, Dhondt L, De Buyzere M, Delanghe J . Increased urinary neutrophil gelatinase associated lipocalin in urinary tract infections and leukocyturia. Clin Chem Lab Med. 2011; 49(6):999-1003. DOI: 10.1515/CCLM.2011.156. View

14.

Nickolas T, Barasch J, Devarajan P . Biomarkers in acute and chronic kidney disease. Curr Opin Nephrol Hypertens. 2008; 17(2):127-32. DOI: 10.1097/MNH.0b013e3282f4e525. View

15.

Lee S, Choi M . Urinary biomarkers for early diabetic nephropathy: beyond albuminuria. Pediatr Nephrol. 2014; 30(7):1063-75. PMC: 4305495. DOI: 10.1007/s00467-014-2888-2. View

16.

Takir M, Unal A, Kostek O, Bayraktar N, Demirag N . Cystatin-C and TGF-β levels in patients with diabetic nephropathy. Nefrologia. 2016; 36(6):653-659. DOI: 10.1016/j.nefro.2016.06.011. View

17.

Bouvet B, Paparella C, Arriaga S, Monje A, Amarilla A, Almara A . Evaluation of urinary N-acetyl-beta-D-glucosaminidase as a marker of early renal damage in patients with type 2 diabetes mellitus. Arq Bras Endocrinol Metabol. 2014; 58(8):798-801. DOI: 10.1590/0004-2730000003010. View

18.

Chakraborty S, Kaur S, Guha S, Batra S . The multifaceted roles of neutrophil gelatinase associated lipocalin (NGAL) in inflammation and cancer. Biochim Biophys Acta. 2012; 1826(1):129-69. PMC: 3362670. DOI: 10.1016/j.bbcan.2012.03.008. View

19.

Wiesli P, Schwegler B, Spinas G, Schmid C . Serum cystatin C is sensitive to small changes in thyroid function. Clin Chim Acta. 2003; 338(1-2):87-90. DOI: 10.1016/j.cccn.2003.07.022. View

20.

Javanmardi M, Azadi N, Amini S, Abdi M . Diagnostic value of cystatin C for diagnosis of early renal damages in type 2 diabetic mellitus patients: The first experience in Iran. J Res Med Sci. 2015; 20(6):571-6. PMC: 4621651. DOI: 10.4103/1735-1995.165960. View