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Am J Physiol Renal Physiol. 2019 Sep 23. doi: 10.1152/ajprenal.00370.2019. [Epub ahead of print]

Renal SGLT mRNA Expression in Human Health and Disease: A Study in Two Cohorts.

Author information

1
Department of Medicine, Division of Nephrology, University of Toronto, Canada.
2
University of Michigan, Computational Medicine and Bioinformatics.
3
Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO. Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, United States.
4
Department of Medicine, Division of Nephrology, University of Colorado School of Medicine, United States.
5
Department of Physiology, University of Toronto, Canada.
6
Medicine, University Health Network, University of Toronto.
7
United States.

Abstract

BACKGROUND:

Pharmacological SGLT2 inhibition is being examined as a renal protection strategy in non-diabetic chronic kidney disease (CKD). We quantified renal sodium-glucose linked cotransporter (SGLT) mRNA expression in healthy controls (HC), glomerulonephritis (GN) and diabetic kidney disease (DKD) to identify differences in expression across a spectrum of renal diseases.

METHODS:

SGLT1 and SGLT2 mRNA expression in renal tubules and glomeruli, obtained using microdissection and microarray techniques, were evaluated in two large cohorts. The European Renal cDNA bank (ERCB) included HC, GN, and DKD (98 glomeruli and 93 tubulointerstitium). The Nephrotic Syndrome Study Network (NEPTUNE) cohort included 124 adults with membranous nephropathy (MN), minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS) and IgA nephropathy (IgAN).

RESULTS:

Within ERCB, SGLT2 tubular and glomerular log2-mRNA expression significantly differed across HC, GN and DKD (p=0.0009 and p=0.0004), with highest expression in HC. Within NEPTUNE, there were no differences in SGLT log2-mRNA expression across GN subtypes. Tubular SGLT2 log2-mRNA expression positively correlated with estimated glomerular filtration rate (eGFRMDRD) and glycated hemoglobin (A1c) (r=0.33 & 0.34, p<0.05); and inversely correlated with interstitial fibrosis (r=-0.21, p<0.05).

CONCLUSIONS:

SGLT2 mRNA expression was lower in DKD compared to HC or GN, and inversely related to interstitial fibrosis. The relationships between SGLT mRNA, protein expression, and transporter activity requires further elucidation.

KEYWORDS:

Diabetic Kidney Disease; Glomerulonephritis; SGLT

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