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Abstract: PO0788

Urinary Biomarkers for Prediction of Estimated GFR Decline in Patients with Type 2 Diabetes and Preserved Kidney Function

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Unoki-Kubota, Hiroyuki, Kokuritsu Kokusai Iryo Kenkyu Center Kenkyujo, Shinjuku-ku, Tokyo, Japan
  • Ito, Emi, Kokuritsu Kokusai Iryo Kenkyu Center Kenkyujo, Shinjuku-ku, Tokyo, Japan
  • Hirano, Daishi, Tokyo Jikeikai Ika Daigaku, Minato-ku, Tokyo, Japan
  • Imasawa, Toshiyuki, National Hospital Organization Chiba-Higashi National Hospital, Chiba, Japan
  • Kajio, Hiroshi, Kokuritsu Kokusai Iryo Kenkyu Center Byoin, Shinjuku-ku, Tokyo, Japan
  • Yamashita, Shigeo, Tokyo Yamate Medical Center, Shinjuku-ku, Tokyo, Japan
  • Fukazawa, Yuka, JR Tokyo Sogo Byoin, Shibuya-ku, Tokyo, Japan
  • Kaburagi, Yasushi, Kokuritsu Kokusai Iryo Kenkyu Center Kenkyujo, Shinjuku-ku, Tokyo, Japan
Background

We have previously performed a urinary proteomic analysis of patients with diabetic kidney disease (DKD) and identified the differentially excreted proteins in the patients with DKD (Diabetes Res Clin Pract. 2019; 147:37-46). In this study, we evaluated the association of the differentially excreted proteins with an annual decline in estimated glomerular filtration (eGFR) in patients with type 2 diabetes (T2D) and preserved kidney function.

Methods

In a prospective, observational cohort study, 392 Japanese patients with T2D and baseline eGFR ≥ 60 ml/min/1.73m2 were followed over one year (mean period 5.5 years; IQR 3.9 – 7.3). Linear regression was used to estimate participants’ annual decline rate in eGFR over time. We defined subjects with an annual eGFR decline ≥ 5% per year as rapid decliner and the eGFR decline < 5% as slow decliner. Of the 392 participants, 218 patients were randomly selected and baseline levels of 75 urinary proteins were measured by multiple reaction monitoring (MRM) analysis.

Results

The study population had a median age of 59.0 years (IQR, 56.3 – 58.5) and 78.0% were male. The median duration of diabetes was 10.0 years (IQR, 9.8 – 12.0). During the follow-up period, 44 patients had a rapid decline in eGFR. Median eGFR decline was -6.51% (IQR, -8.54 – -6.47) and -1.29% (IQR, -1.43 – -0.65) per year in rapid decliner and slow decliner, respectively. Compared with slow decliner, rapid decliner had higher HbA1c level and lower levels of HDL-cholesterol (HDL-c), Hb, and Hct at baseline, however, their differences were not significant. In the MRM analysis, we found that 11 urinary proteins were differentially excreted in rapid decliner compared to the urinary proteins of slow decliner (P < 0.05). Multivariable logistic regression models revealed that 4 urinary proteins and Hb were independent predictors of annual decline in eGFR adjusted by age, HbA1c, HDL-c, eGFR, and urinary albumin-to-creatinine ratio (P < 0.005). When combining the 4 urinary protein levels, an area under the ROC curve for the detection of rapid decliner was 0.781 (95% CI 0.709 – 0.852).

Conclusion

Our findings highlight the important effect of 4 urinary proteins as independent predictors of a rapid decline in eGFR in patients with T2D and preserved kidney function.

Funding

  • Government Support – Non-U.S.