Phenyl Sulfate Predicts Five-Year Albumin-to-Creatinine Ratio (ACR) Deterioration and eGFR Decline in Diabetic Kidney Disease

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Background: Diabetic kidney disease (DKD) occurs in approximately 20-30% of all diabetic patients and represents a major cause of end-stage renal disease (ESRD). 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: As we previously reported (Kikuchi K. et al. Nat. Commun. 2019), serum phenyl sulfate (PS), a uremic toxin derived from intestinal bacteria, level significantly related with the basal albuminuria level in a cohort of diabetic patients (UCARE study, n=362). In addition, logistic regression analysis showed among known albumin-creatinine-ratio (ACR) predictive factors, PS was the only factor which significantly related 2-year progression of albuminuria especially in patients with microalbuminuria. On the other hand, IS, PCS, TMAO which are well-known as gut derived uremic solutes as well as PS were not significantly correlated with the 2-year ACR deterioration. Similar results were obtained in an analysis using urinary PS concentration and Cr corrected values. These data suggested that PS may have a potential as important predictive marker of DKD. Results: In the present study, we performed a new correlation analysis between serum PS concentration and the ACR deterioration and the eGFR (mL/60min/1.73m2) decline, a measure of DKD progression, using 5-year long-term clinical data from the UCARE cohort. Baseline serum PS concentrations were divided into quartiles and analyzed for correlation between elevated serum PS concentrations and the ACR and eGFR exacerbations. Analysis using serum PS and clinical data from baseline to 5 years showed that the 5-year ACR deterioration was significantly higher in Q2 and Q3 compared to Q1, as well as a significant increase in eGFR decline (eGFR decrease of 30% or more or eGFR<15). These data shows that higher serum PS concentration at baseline significantly correlated with the 5-year ACR deterioration, and the 5-year eGFR decline. Conclusion: It was suggested that blood PS could be a new predictive marker of renal prognosis in DKD. Funding: Government Support – Non-U.S.

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