What is increased preglomerular resistance?

Increased Preglomerular Resistance: Pathophysiology and Clinical Implications

Increased preglomerular resistance is a hemodynamic condition characterized by constriction of blood vessels before the glomerulus, primarily affecting the afferent arterioles and other preglomerular vessels, which reduces glomerular filtration rate by decreasing glomerular capillary pressure and renal blood flow. 1

Anatomy and Physiology

Preglomerular resistance occurs in vessels that supply blood to the glomerulus, including:

• Interlobar arteries
• Arcuate arteries
• Interlobular arteries
• Afferent arterioles

While the predominant source of postglomerular resistance is the efferent arteriole, preglomerular resistance is distributed among all preglomerular vessels 2. This distribution allows for differential regulation of blood flow to different nephron populations.

Pathophysiological Mechanisms

Increased preglomerular resistance can occur through several mechanisms:

1. Vasoconstriction: Intense outer cortical vasoconstriction leads to marked increases in preglomerular resistance, causing significant reductions in renal blood flow 3

2. Structural changes: In chronic conditions like hypertension, structural adaptations in preglomerular vessels can occur as a protective mechanism 4

3. Hormonal regulation: Vasoactive hormones can differentially regulate preglomerular vessels, with mediators of inflammation selectively constricting interlobar and arcuate arteries 2

Clinical Significance

1. Acute Renal Failure

In oliguric acute renal failure, intense preglomerular vasoconstriction causes:

• 50-80% reduction in renal blood flow
• Significant decrease in glomerular filtration rate
• This extreme preglomerular constriction may be accompanied by postglomerular vascular relaxation 3

2. Hypertension

In essential hypertension:

• Glomerular filtration rate remains normal or elevated
• Renal blood flow tends to be lower
• Filtration fraction increases
• Preglomerular resistance determines how much pressure is transmitted to glomerular capillaries 5

Increased preglomerular resistance can actually be protective in hypertension by preventing transmission of high systemic pressure to glomerular capillaries 4.

3. Effects of Medications

ACE Inhibitors and ARBs

These medications:

• Preferentially dilate the efferent arteriole
• Reduce intraglomerular pressure while maintaining GFR 6
• Can cause acute decline in renal function in patients with bilateral renal artery stenosis 6

When ACE inhibitors are initiated in patients with heart failure:

• Renal function can deteriorate acutely
• This occurs due to reduction in angiotensin II levels, which affects the balance between afferent and efferent arteriolar tone 1

Diagnostic Considerations

Renal artery duplex ultrasonography can be used to measure renal artery resistive index (RRI), which provides information about resistance in the renal vasculature. An increased RRI suggests structural abnormalities in small blood vessels of the kidney 1.

Clinical Implications

1. Renal Artery Stenosis: Causes increased preglomerular resistance and can lead to renovascular hypertension. When treated with ACE inhibitors, patients with bilateral renal artery stenosis may experience acute renal failure due to inability to maintain glomerular filtration pressure 1

2. Obesity and Kidney Disease: In obesity with reduced nephron mass, afferent arteriole vasodilation occurs to increase single-nephron GFR. This vasodilation impairs autoregulation and allows transmission of elevated systemic blood pressures to glomerular capillaries, potentially causing kidney damage 1

3. Acute Kidney Injury: In acute kidney injury, the relationship between pre- and postglomerular resistance is crucial. Unless cortical ischemia reflects precisely matched increases in pre- and postglomerular resistances, filtration failure is inevitable in vasomotor nephropathy 3

Therapeutic Considerations

When treating conditions involving altered preglomerular resistance:

1. Antihypertensive therapy: The choice of antihypertensive drugs influences progression of renal function based on their effect on glomerular capillary pressure 5

2. ACE inhibitors/ARBs: These are first-line agents for blood pressure management in kidney disease as they preferentially dilate the efferent arteriole, reducing intraglomerular pressure 6

3. Monitoring: A small increase in serum creatinine (up to 30%) is acceptable after starting ACE inhibitors/ARBs, but discontinuation is necessary if kidney function continues to worsen 6

Pitfalls and Caveats

1. ACE inhibitors and ARBs should be used with caution in:

   • Bilateral renal artery stenosis
   • Stenosis in a solitary kidney
   • Advanced renal insufficiency (due to risk of hyperkalemia)

2. Combining ACE inhibitors with ARBs increases risks of hyperkalemia and acute kidney injury without additional benefit 6

3. In patients with heart failure receiving diuretic therapy, ACE inhibitors may cause acute renal failure due to altered preglomerular resistance and reduced renal perfusion pressure 1