Podocyturia parallels proximal tubule dysfunction in type 2 diabetes mellitus patients independently of albuminuria and renal function decline: A cross-sectional study

J Diabetes Complications. 2017 Sep;31(9):1444-1450. doi: 10.1016/j.jdiacomp.2017.01.007. Epub 2017 Jan 20.

Abstract

Aims: Detection of podocytes in the urine of patients with type 2 diabetes may indicate severe injury to the podocytes. In the course of type 2 diabetes the proximal tubule is involved in urinary albumin processing. We studied the significance of podocyturia in relation with proximal tubule dysfunction in type 2 diabetes.

Methods: A total of 86 patients with type 2 diabetes (34-normoalbuminuria; 30-microalbuminuria; 22-macroalbuminuria) and 28 healthy subjects were enrolled in the study and assessed concerning urinary podocytes, podocyte-associated molecules, and biomarkers of proximal tubule dysfunction. Urinary podocytes were examined in cell cultures by utilizing monoclonal antibodies against podocalyxin and synaptopodin.

Results: Podocytes were detected in the urine of 10% of the healthy controls, 24% of the normoalbuminuric, 40% of the microalbuminuric, and 82% of the macroalbuminuric patients. In multivariate logistic regression analysis, urinary podocytes correlated with urinary albumin:creatinine ratio (p=0.006), urinary nephrin/creat (p=0.001), urinary vascular endothelial growth factor/creat (p=0.001), urinary kidney injury molecule-1/creat (p=0.003), cystatin C (p=0.001), urinary advanced glycation end-products (p=0.002), eGFR (p=0.001).

Conclusions: In patients with type 2 diabetes podocyturia parallels proximal tubule dysfunction independently of albuminuria and renal function decline. Advanced glycation end-products may impact the podocytes and the proximal tubule.

Keywords: Advanced glycation end-products; Albuminuria; Podocyturia; Proximal tubule; Renal function.

MeSH terms

  • Albuminuria* / complications
  • Albuminuria* / pathology
  • Albuminuria* / physiopathology
  • Albuminuria* / urine
  • Case-Control Studies
  • Cells, Cultured
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Diabetes Mellitus, Type 2 / urine*
  • Diabetic Nephropathies / complications
  • Diabetic Nephropathies / pathology
  • Diabetic Nephropathies / physiopathology
  • Diabetic Nephropathies / urine
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Kidney / pathology
  • Kidney / physiopathology
  • Kidney Function Tests
  • Kidney Tubules, Proximal / pathology
  • Kidney Tubules, Proximal / physiopathology*
  • Male
  • Middle Aged
  • Podocytes / pathology*
  • Urinalysis / methods
  • Urine / cytology*