, Volume 41, Issue 1, pp 82–88 | Cite as

Urinary tubular biomarkers in short-term type 2 diabetes mellitus patients: a cross-sectional study

  • Wen-jin Fu
  • Shi-long Xiong
  • Yao-gao Fang
  • Shu Wen
  • Mei-lian Chen
  • Ren-tang Deng
  • Lei Zheng
  • Shao-bo Wang
  • Lan-fen Pen
  • Qian Wang
Original Article


The purpose of this study was to investigate the prevalence of tubular damage in short-term (less than five years) type 2 diabetes mellitus (T2DM) patients and to explore the correlation between tubular markers and their relationship with renal indices at different stages of diabetic nephropathy. A group of 101 short-term T2DM patients and 28 control subjects were recruited. Tubular markers, such as neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-β-d-glucosaminidase (NAG), and kidney injury molecule 1 (KIM-1), as well as urinary albumin excretion were measured in voided urine. Glomerular filtration rate (GFR) was estimated via Macisaac’s formula. The patients were further categorized into three groups, namely, the normoalbuminuria, microalbuminuria, and macroalbuminuria groups, according to their urine albumin/creatinine ratio (UACR). Urinary tubular markers were compared and their correlations with renal indices [UACR and estimated GFR (eGFR)] were analyzed among the different diabetic groups. Compared with the control group, Urinary NGAL [median (IQR)][83.6(41.4−138.7) μg/gcr vs. 32.9(26.1−64.5) μg/gcr], NAG [13.5(8.7−17.9) U/gcr vs. 7.6(6.5−13.0) U/gcr] and KIM-1 [120.0(98.4−139.9) ng/gcr vs. 103.1(86.8−106.2) ng/gcr] in the T2DM were all markedly increased. For all patients, urinary NGAL had stronger positive correlations with UACR than NAG (R = 0.556 vs. 0.305, both P < 0.05). In addition, only urinary NGAL showed a negative correlation with eGFR (R = −0.215, P < 0.05). Urinary KIM-1, however, showed no significant difference among the three T2DM groups and did not correlate with either UACR or eGFR. As UACR increased from the normoalbuminuria to the last macroalbuminuria group, all of the markers increased. However, only the concentrations of NGAL were statistically different among the three diabetic groups. The correlation between the tubular markers and their relationships with the renal indices differed markedly among the three T2DM groups. In conclusion, these results suggest that tubular damage is common in short-term T2DM patients. Urinary NGAL may be a promising early marker for monitoring renal impairment in short-term T2DM patients.


Tubular markers Type 2 diabetes mellitus Diabetic nephropathy Microalbuminuria 



This study was supported by the funds from the Scientific and Technological Projects of Dongguan city (200910515000104), Guangdong province, china, P. R.

Conflict of interest

Nothing to declare.


  1. 1.
    M. Krolewski, P.W. Eggers, J.H. Warram, Magnitude of end-stage renal disease in IDDM: a 35 year follow-up study. Kidney Int. 50, 2041–2046 (1996)PubMedCrossRefGoogle Scholar
  2. 2.
    M. Bojestig, H.J. Arnqvist, G. Hermansson et al., Declining incidence of nephropathy in insulin-dependent diabetes mellitus. N. Engl. J. Med. 330, 15–18 (1994)PubMedCrossRefGoogle Scholar
  3. 3.
    P.A. Sarafidis, P.C. Stafylas, P.I. Georgianos et al., Effect of thiazolidinediones on albuminuria and proteinuria in diabetes: a meta-analysis. Am. J. Kidney Dis. 55, 835–847 (2010)PubMedCrossRefGoogle Scholar
  4. 4.
    J.L. Gross, M.J. de Azevedo, S.P. Silveiro et al., Diabetic nephropathy: diagnosis, prevention, and treatment. Diabetes Care 28, 164–176 (2005)PubMedCrossRefGoogle Scholar
  5. 5.
    V.S. Vaidya, M.A. Niewczas, L.H. Ficociello et al., Regression of microalbuminuria in type 1 diabetes is associated with lower levels of urinary tubular injury biomarkers, kidney injury molecule-1, and N-acetyl-β-d-glucosaminidase. Kidney Int. 79, 464–470 (2011)PubMedCrossRefGoogle Scholar
  6. 6.
    G. Jerums, S. Panagiotopoulos, E. Premaratne et al., Integrating albuminuria and GFR in the assessment of diabetic nephropathy. Nat. Rev. Nephrol. 5, 397–406 (2009)PubMedCrossRefGoogle Scholar
  7. 7.
    A. Phillips, U. Janssen, J. Floege, Progression of diabetic nephropathy, Insights from cell culture studies and animal models. Kidney Blood Press Res. 22, 81–97 (1999)PubMedCrossRefGoogle Scholar
  8. 8.
    R.E. Gilbert, M.E. Cooper, The tubulointerstitium in progressive diabetic kidney disease: more than an aftermath of glomerular injury? Kidney Int. 56, 1627–1637 (1999)PubMedCrossRefGoogle Scholar
  9. 9.
    M. von Eynatten, M. Baumann, U. Heemann et al., Urinary L-FABP and anaemia: distinct roles of urinary markers in type diabetes. Eur. J. Clin. Invest. 40, 95–102 (2010)CrossRefGoogle Scholar
  10. 10.
    S.E. Nielsen, T. Sugaya, L. Tarnow et al., Tubular and glomerular injury in diabetes and the impact of ACE inhibition. Diabetes Care 32, 1684–1688 (2009)PubMedCrossRefGoogle Scholar
  11. 11.
    K. Damman, D.J. Van Veldhuisen, G. Navis et al., Tubular damage in chronic systolic heart failure is associated with reduced survival independent of glomerular filtration rate. Heart 96, 1297–1302 (2010)PubMedCrossRefGoogle Scholar
  12. 12.
    D. Bolignano, V. Donato, G. Coppolino et al., Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of kidney damage. Am. J. Kidney Dis. 52, 595–605 (2008)PubMedCrossRefGoogle Scholar
  13. 13.
    J. Mishra, Q. Ma, C. Kelly et al., Kidney NGAL is a novel early marker of acute injury following transplantation. Pediatr. Nephrol. 21, 856–863 (2006)PubMedCrossRefGoogle Scholar
  14. 14.
    C. Bazzi, C. Petrini, V. Rizza et al., Urinary N-acetyl-beta-glucosaminidase excretion is a marker of tubular cell dysfunction and a predictor of outcome in primary glomerulonephritis. Nephrol. Dial. Transplant. 17, 1890–1896 (2002)PubMedCrossRefGoogle Scholar
  15. 15.
    O. Liangos, M.C. Perianayagam, V.S. Vaidya et al., Urinary N-acetyl-beta-(d)- glucosaminidase activity and kidney injury molecule-1 level are associated with adverse outcomes in acute renal failure. J. Am. Soc. Nephrol. 18, 904–912 (2007)PubMedCrossRefGoogle Scholar
  16. 16.
    H.K. Kang, D.K. Kim, B.H. Lee et al., Urinary N-acetyl-beta-d-glucosaminidase and malondialdehyde as a markers of renal damage in burned patients. J. Korean Med. Sci. 16, 598–602 (2001)PubMedGoogle Scholar
  17. 17.
    F. Waanders, M.M. van Timmeren, C.A. Stegeman et al., Kidney injury molecule-1 in renal disease. J. Pathol. 220, 7–16 (2010)PubMedCrossRefGoogle Scholar
  18. 18.
    T. Ichimura, J.V. Bonventre, V. Bailly et al., Kidney injury molecule-1 (KIM-1), a putative epithelial cell adhesion molecule containing a novel immunoglobulin domain, is up-regulated in renal cells after injury. J. Biol. Chem. 273, 4135–4142 (1998)PubMedCrossRefGoogle Scholar
  19. 19.
    T. Ichimura, C.C. Hung, S.A. Yang et al., Kidney injury molecule-1: a tissue and urinary biomarker for nephrotoxicant-induced renal injury. Am. J. Physiol. Renal. Physiol. 286, F552–F563 (2004)PubMedCrossRefGoogle Scholar
  20. 20.
    E.W. Kuehn, K.M. Park, S. Somlo et al., Kidney injury molecule-1 expression in murine polycystic kidney disease. Am. J. Physiol. Renal. Physiol. 283, F1326–F1336 (2002)PubMedGoogle Scholar
  21. 21.
    V.S. Vaidya, V. Ramirez, T. Ichimura et al., Urinary kidney injury molecule-1: a sensitive quantitative biomarker for early detection of kidney tubular injury. Am. J. Physiol. Renal. Physiol. 290(2), F517–F529 (2006)PubMedCrossRefGoogle Scholar
  22. 22.
    J. Surendar, S. Anuradha, B. Ashley et al., Cystatin C and cystatin glomerular filtration rate as markers of early renal disease in Asian Indian subjects with glucose intolerance (CURES-32). Metab. Syndr. Relat. Disord. 7, 419–425 (2009)PubMedCrossRefGoogle Scholar
  23. 23.
    R.J. Macisaac, C. Tsalamandris, M.C. Thomas et al., Estimating glomerular filtration rate in diabetes: a comparison of cystatin-C- and creatinine-based methods. Diabetologia 49, 1686–1689 (2006)PubMedCrossRefGoogle Scholar
  24. 24.
    E. Brocco, P. Fioretto, M. Mauer et al., Renal structure and function in non-insulin dependent diabetic patients with microalbuminuria. Kidney Int. 63, S40–S44 (1997)Google Scholar
  25. 25.
    M. Dalla, Vestra, A. Saller, E. Bortoloso et al., Structural involvement in type 1 and type 2 diabetic nephropathy. Diabetes. Metab. 26(Suppl), 8–14 (2000)Google Scholar
  26. 26.
    Y. Yu, H. Jin, D. Holder et al., Biomarkers of kidney tubule injury: urinary trefoil factor 3 and albumin. Nat. Biotechnol. 28, 470–477 (2010)PubMedCrossRefGoogle Scholar
  27. 27.
    L.M. Russo, R.M. Sandoval, S.B. Campos et al., Impaired tubular uptake explains albuminuria in early diabetic nephropathy. J. Am. Soc. Nephrol. 20, 489–494 (2009)PubMedCrossRefGoogle Scholar
  28. 28.
    Y.C. Ma, L. Zuo, J.H. Chen et al., Modified glomerular filtration rate estimating equation for Chinese patients with chronic kidney disease. J. Am. Soc. Nephrol. 17, 2937–2944 (2006)PubMedCrossRefGoogle Scholar
  29. 29.
    P. Devarajan, Emerging urinary biomarkers in the diagnosis of acute kidney injury. Expert. Opin. Med. Diagn. 2(4), 387–398 (2008)PubMedCrossRefGoogle Scholar
  30. 30.
    S.E. Nielsen, K.J. Schjoedt, A.S. Astrup et al., 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. 27, 1144–1150 (2010)PubMedCrossRefGoogle Scholar
  31. 31.
    S.E. Nielsen, S. Andersen, D. Zdunek et al., Tubular markers do not predict the decline in glomerular filtration rate in type 1 diabetic patients with overt nephropathy. Kidney Int. 79, 1113–1118 (2011)PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Wen-jin Fu
    • 1
    • 2
  • Shi-long Xiong
    • 2
  • Yao-gao Fang
    • 1
  • Shu Wen
    • 3
  • Mei-lian Chen
    • 1
  • Ren-tang Deng
    • 1
  • Lei Zheng
    • 2
  • Shao-bo Wang
    • 4
  • Lan-fen Pen
    • 1
  • Qian Wang
    • 2
  1. 1.Department of Laboratory, Affiliated Houjie HospitalGuangdong Medical CollegeDongguanChina
  2. 2.Department of Laboratory Medicine CentreSouthern Medical UniversityGuangzhouChina
  3. 3.Department of Obstetrics and Gynecology, Molecular and Human GeneticsBaylor College of MedicineHoustonUSA
  4. 4.Department of Endocrinology, Affiliated Houjie HospitalGuangdong Medical CollegeDongguanChina

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