Clinical and Experimental Nephrology

, Volume 23, Issue 1, pp 56–64 | Cite as

Peptiduria: a potential early predictor of diabetic kidney disease

  • Krishnamurthy P. GudehithluEmail author
  • Peter D. Hart
  • Jane Vernik
  • Periannan Sethupathi
  • George Dunea
  • Jose A. L. Arruda
  • Ashok K. Singh
Original article



To protect the kidney effectively with medication in type 2 diabetics, it is crucial to identify such at-risk patients early for treatment. We investigated whether peptiduria precedes proteinuria (the earliest urinary marker in our model), and thereby serve as an early predictor of diabetic nephropathy.


A longitudinal study was performed in a rat model of diabetic nephropathy. Peptides, defined as degradation products of proteins of < 13 kD size, were quantified by a previously validated method using a combination of Lowry and Biorad protein assays. Peptides in urine were also confirmed by chromatographically separating low molecular weight fractions from urine and quantifying albumin fragments in these fractions by enzyme immunoassay. Also, the mechanism of peptiduria was addressed by measuring acid phosphatase, a marker of lysosomal activity, in urine and on kidney sections (histochemically).


In rats with diabetic nephropathy, proteinuria occurred after 12 weeks of diabetes, while peptiduria occurred as early as 2 weeks after diabetes. Peptiduria was confirmed by showing that the chromatographically separated low molecular weight fractions of urine containing albumin fragments is in proportion to the level of peptiduria. The time course of peptiduria paralleled the increase in urinary acid phosphatase suggesting that the mechanism of early peptiduria could be due to upregulation of lysosomal enzyme activity in the tubules.


Our results showing that peptiduria precedes proteinuria in diabetic nephropathy provide a compelling rationale to perform a prospective human clinical trial to investigate whether peptiduria can serve as an early predictor of diabetic nephropathy.


Proteinuria Diabetic nephropathy Peptiduria Acid phosphatase Histochemistry 



The authors wish to acknowledge the technical help of Dr. Lev Rappoport and Ms. Anu Hakimiyan for histological processing of tissues.

Author contributions

I hereby agree that all the authors read the manuscript and agreed with the content.


Financial support for the work was from Hektoen Institute for Medicine, Chicago IL (Grant no. 1994-00107).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interest.

Supplementary material

10157_2018_1620_MOESM1_ESM.docx (15 kb)
Supplementary material 1 (DOCX 14 KB)


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Copyright information

© Japanese Society of Nephrology 2018

Authors and Affiliations

  • Krishnamurthy P. Gudehithlu
    • 1
    Email author
  • Peter D. Hart
    • 1
    • 2
    • 4
  • Jane Vernik
    • 1
    • 2
  • Periannan Sethupathi
    • 3
  • George Dunea
    • 1
    • 3
    • 4
  • Jose A. L. Arruda
    • 1
    • 3
    • 4
  • Ashok K. Singh
    • 1
    • 3
    • 4
  1. 1.Division of NephrologyJohn H. Stroger, Jr. Hospital of Cook County (JSH)ChicagoUSA
  2. 2.Department of Internal MedicineRush University Medical CollegeChicagoUSA
  3. 3.Section of NephrologyUniversity of Illinois at ChicagoChicagoUSA
  4. 4.The Hektoen Institute of MedicineChicagoUSA

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