Serum cystatin C and urinary enzymes as screening markers of renal dysfunction in diabetic patients

J Nephrol. Sep-Oct 2005;18(5):559-67.


Background: In clinical practice, the assessment and follow-up of early renal dysfunction is important in diabetic nephropathy. Therefore, this study was designed to determine whether the serum cystatin C (Cys C) and activities of some tubular enzymes could be used as screening markers for renal dysfunction in diabetic patients.

Methods: Serum Cys C levels and urinary activities of N-acetyl-b-D-glucosaminidase (NAG), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) and whole blood glycolyse hemoglobin (HbA1C) were measured in 56 diabetic patients and 20 healthy subjects (controls). The results were compared with serum creatinine (Cr) and creatinine clearance (CCr), which were measured and estimated with the Cockcroft-Gault formula (CCG) and 24-hr urine microalbuminuria (MAU). We examined the influence of albuminuria, HbA1C and CCr levels of patients on the levels of the analyzed parameters. Sensitivity and specificity for the diagnosis of renal impairment were calculated by a receiver operating characteristics (ROC) curve for serum Cys C, Cr and urinary enzymes.

Results: In normoalbuminurics, only serum Cys C levels and urinary NAG activities were found elevated as compared to controls. In addition to the elevation of serum Cys C levels and urinary activities of NAG, urinary ALP and LDH activities were also found elevated in microalbuminurics. Serum Cys C levels and urinary NAG, ALP, LDH activities started to increase above the normal range when CCr declined and while serum Cr was in the normal range in patients with 50<CCr<80 (grade 2 group). Moreover, these parameters in patients with good metabolic control were significantly lower than in patients with poor metabolic control. There was a significant positive correlation between serum Cys C, urinary NAG, LDH, ALP activities and serum Cr levels. However, there was an inverse correlation between serum Cys C, urinary NAG, LDH, ALP and CCr and CCG in diabetic patients. The ROC plot indicated that serum Cys C and urinary NAG and ALP had higher sensitivity than serum Cr and met the criteria for detecting glomerular and tubular dysfunction as screening tests for early diagnosis of diabetic nephropathy.

Conclusion: This study demonstrated that measuring serum Cys C levels and urinary NAG, ALP and LDH activities could be useful as screening markers to follow-up glomerular and tubular dysfunction in diabetic patients.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Acetylglucosaminidase / urine*
  • Adolescent
  • Adult
  • Aged
  • Albuminuria / diagnosis
  • Alkaline Phosphatase / urine*
  • Biomarkers / analysis
  • Clinical Enzyme Tests
  • Creatinine / urine
  • Cystatin C
  • Cystatins / blood*
  • Diabetes Mellitus / diagnosis*
  • Diabetic Nephropathies / diagnosis*
  • Female
  • Glycated Hemoglobin A / analysis
  • Humans
  • Kidney Tubules / enzymology
  • L-Lactate Dehydrogenase / urine*
  • Male
  • Middle Aged


  • Biomarkers
  • CST3 protein, human
  • Cystatin C
  • Cystatins
  • Glycated Hemoglobin A
  • Creatinine
  • L-Lactate Dehydrogenase
  • Alkaline Phosphatase
  • Acetylglucosaminidase