REN and Hyperinsulinemia: In the kidney, insulin and hyperinsulinemia increase tubular sodium reabsorption and glomerular hyperfiltration, creating intraglomerular hypertension and mesangial expansion, which in turn promote proteinuria and progressive loss of renal function (31).Moreover, IR activates the sympathetic nervous system and the renin–angiotensin–aldosterone system, causing elevated blood pressure, increased volume load, and further hemodynamic stress on both the heart and kidneys.