RT Journal Article SR Electronic T1 Methylation pattern of urinary DNA as a marker of kidney function decline in diabetes JF BMJ Open Diabetes Research & Care JO BMJ Open Diab Res Care FD American Diabetes Association SP e001501 DO 10.1136/bmjdrc-2020-001501 VO 8 IS 1 A1 Takeshi Marumo A1 Junichi Hoshino A1 Wakako Kawarazaki A1 Mitsuhiro Nishimoto A1 Nobuhiro Ayuzawa A1 Daigoro Hirohama A1 Masayuki Yamanouchi A1 Yoshifumi Ubara A1 Toshikazu Okaneya A1 Takeshi Fujii A1 Kazunari Yuki A1 Yoshihito Atsumi A1 Atsuhisa Sato A1 Eri Arai A1 Yae Kanai A1 Tatsuo Shimosawa A1 Toshiro Fujita YR 2020 UL http://drc.bmj.com/content/8/1/e001501.abstract AB Introduction Renal tubular injury contributes to the decline in kidney function in patients with diabetes. Cell type-specific DNA methylation patterns have been used to calculate proportions of particular cell types. In this study, we developed a method to detect renal tubular injury in patients with diabetes by detecting exfoliated tubular cells shed into the urine based on tubular cell-specific DNA methylation patterns.Research design and methods We identified DNA methylation patterns specific for human renal proximal tubular cells through compartment-specific methylome analysis. We next determined the methylation levels of proximal tubule-specific loci in urine sediment of patients with diabetes and analyzed correlation with clinical variables.Results We identified genomic loci in SMTNL2 and G6PC to be selectively unmethylated in human proximal tubular cells. The methylation levels of SMTNL2 and G6PC in urine sediment, deemed to reflect the proportion of exfoliated proximal tubular cells due to injury, correlated well with each other. Methylation levels of SMTNL2 in urine sediment significantly correlated with the annual decline in estimated glomerular filtration rate. Moreover, addition of urinary SMTNL2 methylation to a model containing known risk factors significantly improved discrimination of patients with diabetes with faster estimated glomerular filtration rate decline.Conclusions This study demonstrates that patients with diabetes with continual loss in kidney function may be stratified by a specific DNA methylation signature through epigenetic urinalysis and provides further evidence at the level of exfoliated cells in the urine that injury of proximal tubular cells may contribute to pathogenesis of diabetic kidney disease.