Arteriolar Resistance Changes in Nephron Hyperfiltration
In nephron hyperfiltration, afferent arteriolar resistance decreases (causing vasodilation) while efferent arteriolar resistance remains relatively unchanged or increases, resulting in elevated glomerular capillary pressure and increased filtration fraction. 1, 2
Primary Hemodynamic Mechanism
The fundamental driver of glomerular hyperfiltration is preferential afferent arteriolar vasodilation rather than efferent arteriolar changes:
Afferent arteriolar resistance drops significantly in hyperfiltration states, with studies showing resistance values of 914 dyne/s/cm⁵ in hyperfiltrating diabetic patients compared to 1676 dyne/s/cm⁵ in healthy controls 2
Efferent arteriolar resistance remains similar across hyperfiltrating, normofiltrating, and healthy individuals, indicating it is not the primary mechanism 2
This imbalance creates increased glomerular hydrostatic pressure (66 mmHg in hyperfiltration vs. 60 mmHg in controls), which drives the elevated GFR 2
Role of Angiotensin II in Maintaining Hyperfiltration
Angiotensin II plays a critical role by preferentially constricting the efferent arteriole more than the afferent arteriole, which maintains glomerular capillary pressure despite reduced renal perfusion 1:
In chronic kidney disease with surviving nephrons, this adaptive mechanism sustains GFR through single-nephron hyperfiltration 1
The filtration fraction increases because efferent constriction maintains glomerular pressure while renal blood flow may decrease 3
This explains why ACE inhibitors cause predominant efferent arteriolar vasodilation, reversing hyperfiltration and initially reducing GFR by 10-20% 1
Disease-Specific Patterns
In diabetes mellitus, the mechanism involves additional complexity:
Normal adenosine A2a receptor-mediated efferent arteriolar vasodilation is abolished in diabetic kidneys, causing increased efferent resistance that contributes to hyperfiltration 4
The primary driver remains afferent arteriolar vasodilation, with reduced afferent resistance being the dominant hemodynamic abnormality 2
Both euglycemic and hyperglycemic conditions demonstrate these same patterns 2
Clinical Implications for Treatment
Therapeutic interventions target these resistance changes:
RAAS inhibitors (ACE inhibitors/ARBs) reverse hyperfiltration by causing efferent arteriolar vasodilation, reducing glomerular capillary pressure 1
The initial 10-20% GFR decline with ACE inhibitor initiation indicates the drug is exerting its desired renoprotective effect by normalizing intraglomerular pressure 1
SGLT2 inhibitors work through tubuloglomerular feedback mechanisms to increase afferent arteriolar resistance, thereby reducing hyperfiltration 1, 5
Critical Caveat
Avoid ACE inhibitors/ARBs in bilateral renal artery stenosis or volume depletion because when renal perfusion is already compromised, GFR becomes entirely dependent on angiotensin II-mediated efferent constriction—blocking this can precipitate acute renal failure 1
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