Sex differences in solute and water handling in the human kidney: Modeling and functional implications

The kidneys maintain homeostasis by controlling the amount of water and electrolytes in the blood. That function is accomplished by the nephrons, which transform glomerular filtrate into urine by a transport process mediated by membrane transporters. We postulate that the distribution of renal transporters along the nephron is markedly different between men and women, as recently shown in rodents. We hypothesize that the larger abundance of a renal Na⁺ transport in the proximal tubules in females may also better prepare them for the fluid retention adaptations required during pregnancy and lactation. Also, kidneys play a key role in blood pressure regulation, and a popular class of anti-hypertensive medications and angiotensin converting enzymes (ACE) inhibitors have been reported to be less effective in women. Model simulations suggest that the blunted natriuretic and diuretic effects of ACE inhibition in women can be attributed, in part, to their higher distal baseline transport capacity.