Dysregulated nephrin in diabetic nephropathy of type 2 diabetes: A cross sectional study

Belinda Jim, Mythili Ghanta, Andi Qipo, Ying Fan, Peter Y. Chuang, Hillel W. Cohen, Maria Abadi, David Thomas, John Cijiang He

Research output: Contribution to journalArticle

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Abstract

Background: Podocyte specific proteins are dysregulated in diabetic nephropathy, though the extent of their expression loss is not identical and may be subject to different regulatory factors. Quantifying the degree of loss may help identify the most useful protein to use as an early biomarker of diabetic nephropathy. Methodology/Principal Findings: Protein expression of synaptopodin, podocin and nephrin were quantified in 15 Type 2 diabetic renal biopsies and 12 control patients. We found statistically significant downregulation of synaptopodin (P<0.0001), podocin (P = 0.0002), and nephrin (P<0.0001) in kidney biopsies of diabetic nephropathy as compared with controls. Urinary nephrin levels (nephrinuria) were then measured in 66 patients with Type 2 diabetes and 10 healthy controls by an enzyme-linked immunosorbent assay (Exocell, Philadelphia, PA). When divided into groups according to normo-, micro-, and macroalbuminuria, nephrinuria was found to be present in 100% of diabetic patients with micro- and macroalbuminuria, as well as 54% of patients with normoalbuminuria. Nephrinuria also correlated significantly with albuminuria (rho = 0.89, p<0.001), systolic blood pressure (rho = 0.32, p = 0.007), and correlated negatively with serum albumin (rho = -0.48, p<0.0001) and eGFR (rho = -0.33, p = 0.005). Conclusions/Significance: These data suggest that key podocyte-specific protein expressions are significantly and differentially downregulated in diabetic nephropathy. The finding that nephrinuria is observed in a majority of these normoalbuminuric patients demonstrates that it may precede microalbuminuria. If further research confirms nephrinuria to be a biomarker of pre-clinical diabetic nephropathy, it would shed light on podocyte metabolism in disease, and raise the possibility of new and earlier therapeutic targets.

Original languageEnglish
Article numbere36041
JournalPLoS One
Volume7
Issue number5
DOIs
StatePublished - May 17 2012
Externally publishedYes

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diabetic nephropathy
Diabetic Nephropathies
Medical problems
noninsulin-dependent diabetes mellitus
cross-sectional studies
Type 2 Diabetes Mellitus
Cross-Sectional Studies
Podocytes
Biopsy
Biomarkers
Proteins
biopsy
biomarkers
Down-Regulation
Immunosorbents
protein synthesis
kidneys
Blood pressure
Blood Pressure
Kidney

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Jim, B., Ghanta, M., Qipo, A., Fan, Y., Chuang, P. Y., Cohen, H. W., ... He, J. C. (2012). Dysregulated nephrin in diabetic nephropathy of type 2 diabetes: A cross sectional study. PLoS One, 7(5), [e36041]. https://doi.org/10.1371/journal.pone.0036041

Dysregulated nephrin in diabetic nephropathy of type 2 diabetes : A cross sectional study. / Jim, Belinda; Ghanta, Mythili; Qipo, Andi; Fan, Ying; Chuang, Peter Y.; Cohen, Hillel W.; Abadi, Maria; Thomas, David; He, John Cijiang.

In: PLoS One, Vol. 7, No. 5, e36041, 17.05.2012.

Research output: Contribution to journalArticle

Jim, B, Ghanta, M, Qipo, A, Fan, Y, Chuang, PY, Cohen, HW, Abadi, M, Thomas, D & He, JC 2012, 'Dysregulated nephrin in diabetic nephropathy of type 2 diabetes: A cross sectional study', PLoS One, vol. 7, no. 5, e36041. https://doi.org/10.1371/journal.pone.0036041
Jim, Belinda ; Ghanta, Mythili ; Qipo, Andi ; Fan, Ying ; Chuang, Peter Y. ; Cohen, Hillel W. ; Abadi, Maria ; Thomas, David ; He, John Cijiang. / Dysregulated nephrin in diabetic nephropathy of type 2 diabetes : A cross sectional study. In: PLoS One. 2012 ; Vol. 7, No. 5.
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