Is creatinine elevated in patients with renal artery stenosis?

Creatinine Elevation in Renal Artery Stenosis

Creatinine is typically not elevated with unilateral renal artery stenosis but may become elevated in bilateral renal artery stenosis or stenosis to a solitary kidney, particularly when treated with ACE inhibitors or ARBs. 1

Pathophysiology of Renal Function in RAS

Renal artery stenosis (RAS) produces a spectrum of manifestations ranging from:

• Asymptomatic, incidental findings
• Hypertension (renovascular hypertension)
• Renal insufficiency (ischemic nephropathy)

Unilateral vs. Bilateral RAS

• Unilateral RAS:

  • Generally does not cause significant elevation in serum creatinine
  • The contralateral kidney compensates to maintain overall renal function
  • Studies show that while the stenotic kidney's function may decrease, the overall glomerular filtration rate (GFR) typically remains stable 2

• Bilateral RAS or RAS to a solitary kidney:

  • Can lead to significant elevation in serum creatinine
  • No compensatory mechanism available
  • Associated with progressive renal insufficiency 1

Risk Factors for Creatinine Elevation in RAS

1. ACE inhibitor/ARB therapy:

   • 10-20% of patients with RAS will develop an unacceptable rise in serum creatinine when treated with these medications 1
   • This occurs because these medications block the efferent arteriolar vasoconstriction that normally maintains glomerular filtration pressure in the setting of reduced renal perfusion 1

2. Volume depletion:

   • Diuretic use or dehydration can precipitate acute kidney injury in patients with RAS 1
   • Particularly problematic when combined with ACE inhibitors/ARBs

3. Bilateral disease or stenosis to a solitary kidney:

   • Higher risk of developing azotemia compared to unilateral disease 3
   • In one study, significant decrease in creatinine after revascularization was seen in 61% of patients with bilateral stenosis versus 38% with unilateral stenosis 3

4. Disease progression:

   • Progressive atherosclerotic disease can lead to worsening renal function over time 1
   • A subset of medically treated patients develop progressive disease with worsening hypertension and renal insufficiency 1

Clinical Indicators of RAS with Renal Dysfunction

• Unexplained progressive renal dysfunction
• Worsening hypertension with rising creatinine
• Acute kidney injury following initiation of ACE inhibitors/ARBs
• Flash pulmonary edema with renal dysfunction
• Significant asymmetry in kidney size on imaging

Assessment of Kidney Viability in RAS

The KDIGO guidelines provide criteria to assess kidney viability in RAS 1:

Parameter	Nonviable	Likely to be viable
Renal length	<7 cm	>8 cm
Cortical thickness	Loss of corticomedullary differentiation	Cortex distinct (>0.5 cm)
Albumin-creatinine ratio	>300 mg/g	<200 mg/g
Renal resistive index	>0.8	<0.8

Management Considerations

• Medical therapy:

  • First-line approach for most patients with RAS
  • Careful monitoring of renal function is essential, especially when using ACE inhibitors/ARBs
  • A 10-20% increase in serum creatinine may be anticipated and is not necessarily a reason to discontinue therapy 1

• Revascularization indications (KDIGO consensus) 1:

  • Flash pulmonary edema or acute heart failure decompensations
  • Progressive CKD in high-grade bilateral RAS or RAS to a solitary kidney
  • Acute kidney injury due to acute renal artery occlusion or high-grade stenosis
  • Intolerance of ACE inhibitors/ARBs when such therapy is necessary

Common Pitfalls

1. Misattribution of elevated creatinine: Not all creatinine elevations in patients with RAS are due to the stenosis itself; consider other causes of kidney disease.

2. Inappropriate discontinuation of ACE inhibitors/ARBs: A modest rise in creatinine (10-20%) is expected and acceptable when initiating these medications in patients with RAS 1.

3. Unnecessary revascularization: Multiple studies have shown limited benefit of routine revascularization for unilateral RAS without specific indications 4, 5.

4. Failure to recognize bilateral disease: Bilateral RAS has different implications for renal function and treatment compared to unilateral disease 1.

5. Overlooking volume status: Volume depletion can precipitate acute kidney injury in patients with RAS, particularly when combined with ACE inhibitors/ARBs 1.