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Abstract: TH-PO924

Gut Microbiome-Derived Phenyl Sulfate Contributes to Albuminuria in Diabetic Kidney Disease (Part 2)

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Abe, Takaaki, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, MIYAGI, Japan
  • Kikuchi, Koichi, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, MIYAGI, Japan
  • Saigusa, Daisuke, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
  • Mise, Koki, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
  • Nakamura, Tomohiro, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
  • Kopp, Jeffrey B., NIDDK, NIH, Bethesda, Maryland, United States
  • Toyohara, Takafumi, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, MIYAGI, Japan
  • Mishima, Eikan, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, MIYAGI, Japan
  • Suzuki, Takehiro, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, MIYAGI, Japan
  • Hozawa, Atsushi, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
  • Wada, Takashi, Kanazawa University, Ishikawa, Japan
  • Wada, Jun, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
  • Tomioka, Yoshihisa, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan
Background

Diabetic kidney disease (DKD) represents a major cause of ESRD. However, since it is difficult to identify patients who are at risk of progression, specific biomarker is needed.

Methods

362 patients in a multi-center clinical study in diabetic nephropathy (U-CARE) with full data were selected. The plasma PS level was measured by LC–MS/MS. The correlation between the PS level and various factors was calculated using Spearman Rank-Order Correlation. Multiple regression analysis and logistic regression analysis were used to identify the factors independently associated with PS or the development of 2-year ACR deterioration, respectively.

Results

Participants had a mean age of 63.3 years and 56.9% were male. The blood glucose was 154.2 ± 56.4 mg/dl and the HbA1c was 7.2 ± 1.1 %. The eGFR was 73.8 (17.1 – 115.4) ml/min/1.73 m2 and the albumin to creatinine ratio (ACR) was 11.0 (1.0 – 6407.4) mg/gCr. The serum PS level was 3.3 μM (0 – 68.1 μM) and suPAR was 460.8 (142.0. – 2740.2) pg/ml. The basal plasma PS level significantly correlated with ACR, eGFR, age, duration, HbA1c and uric acid, but not with suPAR. Multiple regression analysis revealed that ACR was the only factor that significantly correlated with PS.
By stratified logistic regression analysis, in the microalbuminuria group, PS was the only factor related to the amount of change in the 2-year ACR in all models, with an odds ratio of 2.02 (CI: 1.04-3.92). ROC curve analysis further showed that a combination of suPAR with known factors increased the c-statistics value and the value were further increased with the PS combination.

Conclusion

PS is related to ACR and could predict the 2-year ACR deterioration in DKD patients, especially with microalbuminuria (Nature Commun. 10: 1835, 2019).

Funding

  • Government Support - Non-U.S.