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

Abstract

BACKGROUND\nPharmacological 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.\n\n\nMETHODS\nSGLT1 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).\n\n\nRESULTS\nWithin 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).\n\n\nCONCLUSIONS\nSGLT2 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.