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Kidney Week

Abstract: TH-PO872

Analysis of DNA Repair Factor KAT5 and DNA Methylation Modulators in Urinary Shedding Cells of Patients with Diabetic Kidney Disease

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Hishikawa, Akihito, Keio University School of Medicine, Tokyo, Japan
  • Hayashi, Kaori, Keio University School of Medicine, Tokyo, Japan
  • Itoh, Hiroshi, Keio University School of Medicine, Tokyo, Japan
Background

Diabetic kidney disease (DKD) is the leading cause of ESRD worldwide. Therefore, early diagnosis is needed. We have recently discovered that DNA repair factor KAT5 is decreased in DKD podocytes, which may lead to impaired DNA repair with aberrant DNA methylation (Cell Rep 2019). Here we investigated the expression profiles of KAT5 and DNA methylation modulators in urinary shedding cells of patients with DKD as a potential diagnostic marker.

Methods

60 outpatients who visited the nephrology department at Keio University Hospital were enrolled (Gender [Male 39, Female 21], Age 63±2, patients with diabetes 17 [eGFR 59.4±5.4], patients without diabetes 43 [eGFR 63.9±3.4]). 50ml of urine samples were collected and centrifuged, and mRNA was extracted to analyze the expression of phenotypical markers (nephrin; podocytes, AQP1; proximal tubular cells, AQP2; collecting duct cells) and epigenetic modulators in urine-derived cells by quantitative RT-PCR method as previously described. The association of the marker expression levels with clinical data including presence of diabetes (DM) or hypertension (HT) was investigated using multivariate regression analysis.

Results

Urine KAT5/nephrin was decreased in diabetic patients (p=0.04) consistent with our previous basic study. On the other hand, KAT5/nephrin was increased in HT patients without DM (p=0.08), whereas it decreased in HT patients with DM (p=0.02). In addition, DNA methyltransferase DNMT1, 3A, 3B and DNA demethylation enzyme TET1, 3 expression adjusted with AQP1 or AQP2 respectively, increased in patients with HT. These expression tendencies correlated with the severity of HT especially in AQP1 adjustment. Moreover, DNMT1/AQP1 and DNMT3A/AQP1 had positive correlation with 1-year eGFR reduction rate. Multivariate regression analysis adjusted for proteinuria, age, eGFR and presence of DM also showed that DNMT1/AQP1 was associated with 1-year eGFR decline as the same extent with the presence of DM.

Conclusion

Urine KAT5/nephrin may be a potential diagnostic marker of DKD. Urine DNMT1, 3A/AQP1 is increased in HT patients and associated with 1-year eGFR reduction rate suggesting its possible role as a predictor of renal prognosis.