Skip to main content

Advertisement

Log in

Efficacy of urinary N-acetyl-β-D-glucosaminidase to evaluate early renal tubular damage as a consequence of type 2 diabetes mellitus: a cross-sectional study

  • Original Article
  • Published:
International Journal of Diabetes in Developing Countries Aims and scope Submit manuscript

Abstract

We assessed the prognostic accuracy of urinary N-acetyl-β-D-glucosaminidase (NAG), an early proximal tubular damage marker for the onset of diabetic nephropathy. The study included 491 eligible participants with 76 healthy controls, 194 type 2 diabetes mellitus (T2DM) patients with 0–5, 5–10, 10–15, and 15–20 years of T2DM duration, 71 microalbuminuric patients, 100 diabetic nephropathy patients, and 50 non-diabetic nephropathy patients. Fasting glucose, serum fructosamine, HbA1C, urinary microalbumin, serum creatinine, estimated glomerular filtration rate (eGFR), serum NAG, and urinary NAG were estimated. We compared urinary NAG activity with other well-established markers of diabetic nephropathy like microalbuminuria, eGFR, and serum creatinine. Urinary NAG excretion was increased by 8 and 12 folds in T2DM patients of 10–15 and 15–20 years of diabetes duration (p < 0.0001), respectively, without the appearance of microalbuminuria. The urinary NAG activity increased 16 and 18 fold in moderately increased albuminuria and diabetic nephropathy patients, respectively (p < 0.0001), without any change in non-diabetic nephropathy patients. A cutoff value of 3 U/L of urinary NAG has demonstrated a sensitivity of 96.1 % and a specificity of 100 % discriminating healthy controls from patients with T2DM duration of 10–15 years (AUC 1.000) and 15–20 years (AUC 0.999); microalbuminuria (AUC 0.999), and diabetic nephropathy (AUC 1.000). Urinary NAG excretion gradually increases with the increase in duration of diabetes and appeared much before the microalbuminuria, decreased eGFR, and increased serum creatinine. Thus, the urinary NAG may be considered as a potential site-specific early tubular damage marker leading to diabetic nephropathy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Dronavalli S, Duka I, Bakris GL. The pathogenesis of diabetic nephropathy. Nat Clin Pract Endorinol Metab. 2008;4:444–52.

    Article  CAS  Google Scholar 

  2. Hong CY, Chia KS. Markers of diabetic nephropathy. J Diabetes Complicat. 1998;12:43–60.

    Article  PubMed  CAS  Google Scholar 

  3. Wolf G, Ziyadeh F. Molecular mechanisms of diabetic renal hypertrophy. Kidney Int. 1999;56:393–405.

    Article  PubMed  CAS  Google Scholar 

  4. Phillips AO, Steadman R. Diabetic nephropathy: the central role of renal proximal tubular cells in tubulointerstitial injury. Histol Histopathol. 2002;17:247–52.

    PubMed  CAS  Google Scholar 

  5. Turecky L, Uhlikova E. Diagnostic significance of urinary enzymes in nephrology. Bratisl Lek Listy. 2003;104(1):27–31.

    PubMed  CAS  Google Scholar 

  6. Fukui M, Nakamura T, Ebihara I, Shirato I, Tomino Y, Koide H. ECM gene expression and its modulation by insulin in diabetic rats. Diabetes. 1992;41:1520–7.

    Article  PubMed  CAS  Google Scholar 

  7. Steffes MW, Osterby R, Chavers B, Mauer M. Mesangial expansion as a central mechanism for loss of kidney function in diabetic patients. Diabetes. 1989;38:1077–81.

    Article  PubMed  CAS  Google Scholar 

  8. Caramori ML, Fioretto P, Mauer M. The need for early predictors of diabetic nephropathy risk is albumin excretion rate sufficient? Diabetes. 2000;49:1399–408.

    Article  PubMed  CAS  Google Scholar 

  9. Perrone RD, Madias NE, Levey AS. Serum creatinine as an index of renal function: new insights into old concepts. Clin Chem. 1992;38(10):1933–53.

    PubMed  CAS  Google Scholar 

  10. Belfiore F, Napoli E, Vecchio LL. Serum N-acetyl-beta-glucosaminidase activity in diabetic patients. Diabetes. 1972;21(12):1168–72.

    Article  PubMed  CAS  Google Scholar 

  11. Price RG, Dance N. The cellular distribution of some rat-kidney glycosidases. Biochem J. 1967;105:877–83.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  12. Karakani MA, Haghighi SA, Khansari MG, Hosseini R. Determination of urinary enzymes as a marker of early renal damage in diabetic patients. J Clin Lab Anal. 2007;21:413–7.

    Article  Google Scholar 

  13. Piwowar A, Kordecka MK, Fus I, Warwas M. Urinary activities of cathepsin B, N-acetyl-beta-d-glucosaminidase, and albuminuria in patients with type 2 diabetes mellitus. Med Sci Monit. 2006;12(5):CR210–4.

    PubMed  CAS  Google Scholar 

  14. Bazzi C, Petrini C, Rizza V, Arrigo G, Napodano P, et al. Urinary N-acetyl-b-glucosaminidase excretion is a marker of tubular cell dysfunction and a predictor of outcome in primary glomerulonephritis. Nephrol Dial Transplant. 2002;17:1890–6.

    Article  PubMed  CAS  Google Scholar 

  15. Han W, Waikar S, Johnson A, Betensky R, Dent C, Devarajan P, et al. Urinary biomarkers in the early diagnosis of acute kidney injury. Kidney Int. 2008;73:863–9.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  16. Fu W, Xiong S, Fang Y, Wen S, Chen M, Deng R, et al. Urinary tubular biomarkers in short-term type 2 diabetes mellitus patients: a cross-sectional study. Endocrine. 2012;41:82–8.

    Article  PubMed  CAS  Google Scholar 

  17. Ouchi M, Suzuki T, Hashimoto M, Motoyama M, Ohara M, Suzuki K, et al. Urinary N-acetyl-β-d-glucosaminidase levels are positively correlated with 2-h plasma glucose levels during oral glucose tolerance testing in prediabetes. J Clin Lab Anal. 2012;26:473–80.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  18. Kroll MH, Chesler R, Hagengruber C, Blank DW, Kestner J, Rawe M. Automated determination of urinary creatinine without sample dilution: theory and practice. Clin Chem. 1986;32(3):446–52.

    PubMed  CAS  Google Scholar 

  19. Cockroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16:31–41.

    Article  Google Scholar 

  20. Parker KM, England JD, Da Costa J, Hess RL, Gloldstein DE. Improved colorimetric assay for glycated hemoglobin. Clin Chem. 1981;27(5):669–72.

    PubMed  CAS  Google Scholar 

  21. Horak E, Hopfer SM, Sunderman Jr WF. Spectrophotometric assay for urinary N-acetyl-b-d-glucosaminidase. Clin Chem. 1981;27(7):1180–5.

    PubMed  CAS  Google Scholar 

  22. Lehmann R, Schleicher ED. Molecular mechanism of diabetic nephropathy. Clin Chim Acta. 2000;297:135–44.

    Article  PubMed  CAS  Google Scholar 

  23. Fua WJ, Liang LB, Wang SB, Chen ML, Deng TR, Qin YC, et al. Changes of the tubular markers in type 2 diabetes mellitus with glomerular hyperfiltration. Diabetes Res Clin Pract. 2012;95:105–9.

    Article  Google Scholar 

  24. Kalia K, Sharma S, Mistry K. Non-enzymatic glycosylation of immunoglobulins in diabetic nephropathy. Clin Chim Acta. 2004;347:169–76.

    Article  PubMed  CAS  Google Scholar 

  25. Mohan S, Kalia K, Mannari J. Diabetic nephropathy and associated risk factors for renal deterioration. Int J Diabetes Dev Ctries. 2012;32(1):52–9.

    Article  Google Scholar 

  26. Mohan S, Kalia K, Mannari J. Urinary IgG is a pure strong indicator of diabetic nephropathy than microalbuminuria in type 2 diabetic patients. Int J Diabetes Dev Ctries. 2013;33(1):46–54.

    Article  CAS  Google Scholar 

  27. Barratt J, Topham P. Urine proteomics: the present and future of measuring urinary protein components in disease. CMAJ. 2007;177(4):361–8.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Moresco RN, Sangoi MB, Carvalho J, Tatsch E, Bochi G. Diabetic nephropathy: traditional to proteomic markers. Clin Chim Acta. 2013;421:17–30.

    Article  PubMed  CAS  Google Scholar 

  29. Nauta FL, Boertien WE, Bakker SJ, Goor HV, Oeveren WV, Jong PE, et al. Glomerular and tubular damage markers are elevated in patients with diabetes. Diabetes Care. 2011;34:975–81.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Abate M, Zoja C, Remuzzi G. How does proteinuria cause progressive renal damage? J Am Soc Nephrol. 2006;17:2974–84.

    Article  Google Scholar 

  31. Kalansooriya A, Jennings P, Haddad F, Holbrook I, Whiting PH. Urinary enzyme measurements as early indicators of renal insult in type 2 diabetes. Br J Biomed Sci. 2007;64(4):153–6.

    PubMed  CAS  Google Scholar 

  32. Vestra MD, Masiero A, Roiter AM, Saller A, Crepaldi G, Fioretto P. Is podocyte injury relevant in diabetic nephropathy? Studies in patients with type 2 diabetes. Diabetes. 2003;52:1031–5.

    Article  PubMed  Google Scholar 

  33. Ding H, He Y, Lia K, Yang J, Li X, Lu R, et al. Urinary neutrophil gelatinase-associated lipocalin (NGAL) is an early biomarker for renal tubulointerstitial injury in IgA nephropathy. Cin Immu. 2007;123:227–34.

    Article  CAS  Google Scholar 

  34. Barratt J, Feehally J. IgA nephropathy. J Am Soc Nephrol. 2005;16:2088–97.

    Article  PubMed  CAS  Google Scholar 

  35. Floege J, Feehally J. IgA nephropathy: recent developments. J Am Soc Nephrol. 2000;11:2395–403.

    PubMed  CAS  Google Scholar 

  36. Soler MJ, Mir M, Rodriguez E, OrWla A, Munne A, Vazquez S, et al. Recurrence of IgA nephropathy and Henoch-Schoenlein purpura after kidney transplantation: risk factors and graft survival. Transplant Proc. 2005;37:3705–9.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors are grateful to the Muljibhai Patel Urological Hospital, Nadiad, Gujarat, India, for their support to provide blood and urine samples of patients used for the present study. The authors thank the University Grant Commission, New Delhi, for providing research fellowship to pursue this work.

Conflict of interest

There are no conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kiran Kalia.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Patel, D.N., Kalia, K. Efficacy of urinary N-acetyl-β-D-glucosaminidase to evaluate early renal tubular damage as a consequence of type 2 diabetes mellitus: a cross-sectional study. Int J Diabetes Dev Ctries 35 (Suppl 3), 449–457 (2015). https://doi.org/10.1007/s13410-015-0404-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13410-015-0404-2

Keywords

Navigation