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Abstract: PO0787

The Gut Microbiome-Derived Phenyl Sulfate Is a Novel Predictive Marker and Cause of Albuminuria in Diabetic Kidney Disease

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Kikuchi, Koichi, Tohoku Daigaku, Sendai, Miyagi, Japan
  • Abe, Takaaki, Tohoku Daigaku, Sendai, Miyagi, Japan
Background

Diabetic kidney disease (DKD) is one of the major causes of end-stage renal diseases (ESRD), and it is important to prevent from onset or progression of DKD. However, it is difficult to identify type 2 diabetes patients who are at risk of developing progressive DKD based only on measurements of glomerular filtration rate and albuminuria. Therefore, specific biomarkers are needed for a breakthrough in the good management of DKD.

Methods

Among 777 patinets in a multi-center clinical study in diabetic nephropathy cohort (U-CARE), 362 patients with full data were selected. The plasma PS, PCS, IS and TMAO level were measured by LCMS/MS. The correlation between these level and various factors were calculated using the Spearman Rank-Order Correlation. Multiple regression analysis and a logistic regression analysis were used to identify the factors associated with PS, IS, PCS, TMAO, suPAR, urine acid or the development of 2-year ACR deterioration, respectively.

Results

As we previously reported (Kikuchi et al. Nat. Commun. 2019, ASN 2019), serum PS level significantly related with the basal albuminuria level in U-CARE study. In addition, logistic regression analysis showed among known ACR predictive factors, PS was the only factor which significantly related 2-year progression of albuminuria especially in patients with microalbuminuria. These data suggested that PS may have a potential as important predictive marker of DKD.
Next, we examined the relationship between albuminuria or renal function and IS, PCS, TMAO which were well-known as gut derived uremic solutes as well as PS. In addition, we examined the relationship between albuminuria or renal function and suPAR, uric acid. As a result, IS, PCS, suPAR were inversely correlated with eGFR. PS, IS, suPAR and uric acid were correlated with albuminuria. Among them, PS and uric acid were the factor which significantly correlated with the 2-year albumin-creatinine ratio (ACR) deterioration. Furthermore, we clarified that serum PS concentration level was high even in same patients who are preserved renal function (eGFR>60 ml/min/1.73cm2), and high PS concentration patients were significantly increased 2-year ACR deterioration rate.

Conclusion

PS is predictive marker of albuminuria in the patients with microalbuminuria in DKD patients.