Supplementary Materials and Methods
Transient transfection and cell treatment and Luciferase assay
Cell culture, transient transfection and luciferase assay were performed as described in the main manuscript. The plasmid encoding human sgk-1 promoter-driven luciferase reporter (pSGK1-LUC) was purchased from SwitchGear Genomics (CA, USA). The nuclear factor of activated T cells (NFAT) promoterdriven luciferase reporter (pNFAT-LUC) was purchased from Agilent Technologies (CO, USA). When only pCMX-FLAG-hMR or only pMRE-LUC was transfected, scramble DNA was added to keep DNA concentration at the transfection. Cells were treated with glucocorticoid receptor antagonist (1 μM RU486), androgen receptor antagonist (10 μM flutamide), or mineralocorticoid receptor antagonist (10 μM eplerenone). The activity of the control group was arbitrarily expressed as 1.
Quantitative real-time RT-PCR
Total RNA was isolated using an RNeasy Mini Kit (Qiagen, CA, USA). Reverse transcription and real-time RT-PCR was performed using Step One Plus (Applied Biosystems, CA, USA), TaqMan chemistry, and assay-on-demand primers and probe sets as described previously(Yoshida et al., 2008)⁠. Gene expression of the target sequence was normalized to that of GAPDH as an internal control. The transcript level in the control group was arbitrarily expressed as 1.
Immunohistochemistry of the kidneys
The kidneys were fixed in 4% paraformaldehyde solution and embedded in Tissue-Tek OCT compound (Sakura Finetek, CA, USA)), frozen on dry ice, and cut at 6 μm thickness. Immunostaining was performed on transverse sections. Anti-MR antibody was purchased from Perseus Proteomics (Tokyo,
Japan).
Western blotting
We performed western blotting as described in the main manuscript. Whole kidneys were harvested from 10 weeks old male untreated KKA y mice and C57BL/6J mice.

Supplementary Figures and Legends
Supplementary Fig. 1. The effect of glucose on MR transcriptional activity in cultured mesangial cells.
Cultured mesangial cells were transfected with pMRE-LUC alone (a) or pCMX-FLAG-hMR and pMRE-
LUC (b), incubated under normal glucose (6.67 mM) or high glucose (40 mM) for 24 hours, and performed luciferase reporter assay. When transfected with only pMRE-LUC, the increase of MR activity by aldosterone was reduced, but still existed. Glucose slightly, but not significantly increased MR activity (a).
Glucose-stimulated MR transcriptional activity was not altered by inhibition of GR or AR, but dramatically inhibited by EPL (b). The value of aldo(-) mannitol is expressed as 1. Values are means ± SEM. * P< 0.05 vs. aldo(-) mannitol. # P< 0.05 vs. aldo(+) mannitol.

Supplementary Fig. 2. The effect of glucose on sgk-1 expression in cultured mesangial cells.
Cultured mesangial cells were transfected with pCMX-FLAG-hMR and pSGK1-LUC, incubated under normal glucose (6.67 mM) or high glucose (40 mM) for 24 hours, and performed luciferase reporter assay and real time RT-PCR. Glucose and aldosterone activated sgk-1 promoter in mesangial cells, similar to
MMTV promoter (a). The expression of sgk-1 mRNA was increased in a similar fashion to the promoter activity (b). The value of aldo(-) mannitol is expressed as 1. Values are means ± SEM. * P< 0.05 vs. aldo(-) mannitol. # P< 0.05 vs. aldo(+) mannitol.

Supplementary Fig. 3. The effect of glucose on non-MR related gene expression in cultured mesangial cells.
Cultured mesangial cells were transfected with pCMX-FLAG-hMR and pNFAT-LUC, incubated under normal glucose (6.67 mM) or high glucose (40 mM) for 24 hours, and performed luciferase reporter assay and real time RT-PCR. Glucose and aldosterone did not altered NFAT promoter activity in mesangial cells
(a). The expression of 11β-HSD2 mRNA was neither affected by glucose or aldosterone (b). The value of aldo(-) mannitol is expressed as 1. Values are means ± SEM. * P< 0.05 vs. aldo(-) mannitol. # P< 0.05 vs. aldo(+) mannitol.

Supplementary Fig. 4. The effect of EHT on renal inflammatory gene expression of KKA y mice.
Real-time RT-PCR revealed that KKA y showed overexpression of inflammatory genes such as MCP-1 (a) and TNF-α (b). EHT treatment significantly suppressed mRNA of these genes.

Supplementary Fig. 5. The renal MR expression in KKA y mice.
Immunohistochemistry revealed glomerular MR expression in both BL6 and KKA y mice. Glomerular MR expression was detected mainly in podocytes, but also detected in mesangial cells (arrow). The glomerular expression of MR did not change between BL6 and KKA y (a). The expression of MR in the whole cell lysates of the kidney did not alter between BL6 and KKA y , as detected by Western blotting (b). Bar = 50 μm.
Values are means ± SEM.