Remaining nephrons hyperfilter, which compensates but accelerates decline
Expansion
Intact nephron hypothesis: as nephrons are lost, the survivors behave normally but each handles a larger load.
- Single nephron GFR rises (hyperfiltration)
- Fractional excretion of sodium, potassium and phosphate rises to maintain balance
- Plasma levels stay normal until function is substantially reduced, which is why patients are asymptomatic until late
The cost is glomerular hypertension. Angiotensin II mediated efferent constriction raises intraglomerular pressure, which damages the barrier, causes proteinuria, and leads to focal segmental glomerulosclerosis. Nephron loss then accelerates.
This is the rationale for the mainstays of treatment: ACE inhibitors and angiotensin receptor blockers, which dilate the efferent arteriole, lower intraglomerular pressure and reduce proteinuria, and SGLT2 inhibitors, which restore tubuloglomerular feedback and reduce hyperfiltration.
Both cause an expected initial fall in GFR of up to 25 per cent, which is haemodynamic and not harmful; it reflects the intended reduction in glomerular pressure.