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Peptiduria: a potential early predictor of diabetic kidney disease

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Abstract

Background

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.

Methods

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).

Results

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.

Conclusions

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.

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Acknowledgements

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

Funding

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

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Authors and Affiliations

  1. Division of Nephrology, John H. Stroger, Jr. Hospital of Cook County (JSH), 1900 West Polk Street, Suite 643, Chicago, IL, 60612, USA

    Krishnamurthy P. Gudehithlu, Peter D. Hart, Jane Vernik, George Dunea, Jose A. L. Arruda & Ashok K. Singh

  2. Department of Internal Medicine, Rush University Medical College, Chicago, IL, USA

    Peter D. Hart & Jane Vernik

  3. Section of Nephrology, University of Illinois at Chicago, Chicago, IL, USA

    Periannan Sethupathi, George Dunea, Jose A. L. Arruda & Ashok K. Singh

  4. The Hektoen Institute of Medicine, Chicago, IL, USA

    Peter D. Hart, George Dunea, Jose A. L. Arruda & Ashok K. Singh

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  1. Krishnamurthy P. Gudehithlu
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  2. Peter D. Hart
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  3. Jane Vernik
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  4. Periannan Sethupathi
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  6. Jose A. L. Arruda
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  7. Ashok K. Singh
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Correspondence to Krishnamurthy P. Gudehithlu.

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The authors declare that they have no competing interest.

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Gudehithlu, K.P., Hart, P.D., Vernik, J. et al. Peptiduria: a potential early predictor of diabetic kidney disease. Clin Exp Nephrol 23, 56–64 (2019). https://doi.org/10.1007/s10157-018-1620-0

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  • DOI: https://doi.org/10.1007/s10157-018-1620-0

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