Renal SGLT mRNA expression in human health and disease: a study in two cohorts

Abstract

Pharmacological Na+-glucose linked cotransporter (SGLT)2 inhibition is being examined as a renal protection strategy in nondiabetic chronic kidney disease. We quantified renal 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. mRNA expression of SGLT1 and SGLT2 in renal tubules and glomeruli, obtained using microdissection and microarray techniques, was evaluated in two large cohorts. The European Renal cDNA bank included HC, GN, and DKD (98 glomeruli and 93 tubulointerstitium). The Nephrotic Syndrome Study Network cohort included 124 adults with membranous nephropathy, minimal change disease, focal segmental glomerulosclerosis, and IgA nephropathy. Within the European Renal cDNA bank, SGLT2 tubular and glomerular log2 mRNA expression significantly differed across HC, GN, and DKD ( P = 0.0009 and P = 0.0004), with the highest expression in HC. Within the Nephrotic Syndrome Study Network, there were no differences in SGLT log2 mRNA expression across GN subtypes. Tubular SGLT2 log2 mRNA expression positively correlated with estimated glomerular filtration rate (by the Modification of Diet in Renal Disease Study equation) and glycated hemoglobin ( r = 0.33 and 0.34, P < 0.05) and inversely correlated with interstitial fibrosis ( r = −0.21, P < 0.05). In conclusion, SGLT2 mRNA expression was lower in DKD compared with HC or GN and inversely related to interstitial fibrosis. The relationships between SGLT mRNA, protein expression, and transporter activity require further elucidation.

Comparative analysis of SGLT-2 expression in renal vasculitis and lupus nephritis

“…Although patients with autoimmune diseases were excluded from large renal outcome trials, the use of SGLT-2i in antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and systemic lupus erythematodes (SLE) for nephroprotection has increasingly been emphasised 2–4. While SGLT-2 was studied in diabetic nephropathy and IgA nephropathy (IgAN), the presence of SGLT-2 specifically in renal vasculitis and lupus nephritis has not been described yet 5…”

Kidney ACE2 expression: Implications for chronic kidney disease

“…Kidneys of HLD served as the control group. As per published reports, mRNA levels in the ERCB were derived using Affymetrix GeneChip Human Genome U133A 2.0 and U133 Plus 2.0 arrays [ 32 ].…”

“Greedy Organs Hypothesis” for sugar and salt in the pathophysiology of non-communicable diseases in relation to sodium-glucose co-transporters in the intestines and the kidney

“…On one hand, mRNA and protein expressions of SGLT2 increased in kidney biopsy specimen of type 2 diabetics with nephropathy [ 34 ]. On the other hand, it was reported that SGLT2 mRNA expression in PTs was lower in type 2 diabetic patients than nondiabetic control [ 67 , 68 ]. A study using human kidney biopsy tissue of glomerulonephritis (minimal change disease, membranous nephropathy, focal segmental glomerulosclerosis (FSGS), IgA nephropathy) showed that tubular SGLT2 mRNA expression was correlated positively with eGFR and negatively with interstitial fibrosis [ 68 ].…”

“…On the other hand, it was reported that SGLT2 mRNA expression in PTs was lower in type 2 diabetic patients than nondiabetic control [ 67 , 68 ]. A study using human kidney biopsy tissue of glomerulonephritis (minimal change disease, membranous nephropathy, focal segmental glomerulosclerosis (FSGS), IgA nephropathy) showed that tubular SGLT2 mRNA expression was correlated positively with eGFR and negatively with interstitial fibrosis [ 68 ]. It means that when eGFR is high, SGLT2 is highly expressed and the kidney can become greedy.…”