SGLT2 Inhibitors in Glomerular Hyperfiltration

Summary

Glomerular hyperfiltration is a major risk factor for accelerated glomerular filtration rate (GFR) decline and renal and cardiovascular events despite optimized conservative therapy with blood pressure and blood glucose (in diabetics) lowering medications and inhibitors of the Renin Angiotensin System (RAS) such as Angiotensin Converting Enzyme (ACE) inhibitors and/or Angiotensin Receptor Blockers (ARBs). Progressive GFR decline initiated and sustained by glomerular hyperfiltration in subjects with diabetes, unhealthy obesity, hypertension and other risk factors, is paralleled by progressive glomerulosclerosis and loss of functioning nephrons. The inhibition of the sodium-glucose cotransporter 2 (SGLT2) in the proximal tubular segments of the nephrons appears to be an ideal, specific intervention to inhibit the tubulo-glomerular feedback and ameliorate glomerular hyperfiltration in subjects with absolute or relative hyperfiltration associated with unhealthy obesity or proteinuric chronic kidney disease (CKD). Indeed, by reducing tubular sodium reabsorption, SGLT2 inhibitors may enhance sodium chloride delivery to the macula densa, restore pre-glomerular resistances and therefore limit glomerular hyperperfusion and consequent hyperfiltration. Moreover, because of its natriuretic effects, SGLT2 inhibition therapy might reduce the sodium overload and volume expansion which, along with secondary hypertension, may further contribute to kidney hyperperfusion and glomerular hyperfiltration in obesity and CKD.

Timeline

Start

2021-09-03

Primary completion

2021-09-03

Completion

2021-09-03

Drugs

Indications