Renal and visceral arterial disease

Prevalence

Atherosclerotic renal disease is symptomatic in about 7% of elderly Americans, the incidence increasing with age. The prevalence of asymptomatic disease is higher, with autopsy studies showing renal vascular disease in over 40% of those aged 75 years or older. Atherosclerotic renal vascular disease (ARVD) and RAS are terms used interchangeably; however, the former may be a better term as a high-grade stenosis of the renal artery may not be present in all patients. ARVD is thus a manifestation of generalised atherosclerotic disease; concomitant disease in coronary, carotid and peripheral vascular fields is present in 15–45%. The correlation of ARVD and end-stage renal disease (ESRD) is complex and causality may be difficult to determine in this patient group: selective use of renal revascularisation also shows inconsistent associations with cardiovascular outcomes, renal replacement therapy and death.

Definitions

ARVD occurs with between 50–75% renal artery diameter loss as diagnosed on conventional angiography (gold standard); however, lesions less than 50% may also be associated with significant (15 mmHg) pressure gradients.

Pathophysiology

A haemodynamically significant RAS will lead to a reduction in renal artery perfusion pressure and thus potentially an impairment of renal function simply because of a hydraulic effect, but only in a minority of patients. More commonly, there is a compensatory rise in renin and angiotensin levels in the post-stenotic kidney, constricting the post-glomerular efferent arteriole, which in turn helps to support glomerular capillary hydraulic pressure and filtration rate ( Table 15.1 ). As glomerular perfusion in these patients is critically dependent upon angiotensin II, the risk of developing acute renal failure is significant, especially if the stenosis is bilateral or affects a solitary functioning kidney.

Table 15.1

Pathogenesis of renovascular hypertension

Pathogenetic pathway progression	Stage of renovascular hypertension	Response to intervention
	Renin–angiotensin-dependent phase	Responds to correction of renal artery stenosis/occlusion
	Salt retention phase
	Renin–angiotensin- independent phase	Does not respond to correction of obstructions

Studies in large cohorts of patients with ARVD have shown that there is often poor correlation between the degree of anatomical atheromatous stenosis, glomerular filtration rate (GFR) and overall renal function. ^, Patients with unilateral ARVD can have GFRs that range from normal to stage 5 kidney disease. Nuclear studies in patients with unilateral stenosis reveal that GFR may be the same or even lower in the non-stenotic kidney. This lack of correlation between the severity of renal ischaemic injury and kidney function may explain why renal function often fails to improve significantly after revascularisation despite restoration of renal artery patency. It should also be noted that 1–5% of patients with hypertension are diagnosed to have a significant RAS.

Patients with severe aortic atheroma undergoing arterial surgical or angiographic procedures, thrombolysis or anticoagulation are at risk of developing renal dysfunction secondary to cholesterol emboli.

Clinical presentation

The clinical index of suspicion remains essential in determining an appropriate diagnostic and therapeutic strategy in ARVD. Specific clinical pointers include:

• hypertension, often refractory to treatment; hypertensive crises;

• concomitant cardiovascular disease;

• angiotensin-converting enzyme-induced acute renal impairment;

• ‘flash’ pulmonary oedema (Pickering syndrome);

• vascular bruit, pulse deficit in a smoker;

• ischaemic nephropathy;

• secondary hypoaldosteronism.

Diagnosis ^,

Laboratory investigations other than plasma renin levels are non-specific; their major role is in ruling out other conditions like Conn’s syndrome or a pheochromocytoma. However, they may be used to evaluate the level of nephropathy present – for example, patients with advanced nephropathy indicated by >1 g/day proteinuria have poor outcomes from surgical intervention. Functional studies such as captopril renography and selective renal vein renin sampling have a role in the detection of ARVD, with the potential to predict a blood pressure response to revascularisation or to document the functional significance of RAS.

Duplex scanning is a good initial diagnostic tool; however, problems with operator dependency and body habitus can hinder this. Significant lesions can be identified by measurement of peak systolic velocity (>200 cm/s) in the main renal artery and its branches, along with end diastolic velocity, parenchymal Doppler signals, the presence of post-stenotic turbulence, nature of waveforms, measurement of acceleration times, resistivity index, renal size and the ratio of renal artery to aortic peak systolic velocity of >3.5. Assessment protocols differ between institutions and a standardisation would be clinically useful.

The gold-standard for the imaging of RAS is digital subtraction angiography. One benefit is that intervention may be performed immediately upon diagnosis with this modality. However, given the invasive nature of the study, as well as the nephrotoxic potential of contrast agents, a number of other imaging modalities such as ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) exist with high sensitivity and specificity. CO ₂ angiography also has a limited role in those in whom both MRI and CT angiography (CTA) are contraindicated.

CTA ( Fig. 15.1a ) provides information about the aorta and visceral vessels, neighbouring organs to exclude secondary causes or FMD and is of particular value in patients under consideration for open or endovascular revascularisation. The drawback of CTA is the risk of contrast nephropathy in a patient cohort that is already at risk for renal impairment. Other advances like fusion imaging or cone beam technology may become clinically useful in the future especially when considering endovascular therapy.

An alternative is MRI ( Fig. 15.1b ), but this requires long scan times with comparatively poor image quality. The risk of nephrogenic systemic sclerosis in RAS is significant; gadolinium should be avoided in patients with a GFR of less than 15 mL/min per 1.73 m ² .

Medical management

Medical management is twofold: to promote modification of atherosclerotic risk factors (aspirin, lipid-lowering drugs, cessation of smoking, glycaemic control) and targeted management for hypertension. Involvement of a nephrologist at an early stage is often necessary, as sudden drastic blood pressure reduction may be harmful. All imaging should be done with adequate hydration; the use of other renal protective agents (N-acetyl cysteine) is described but not universally accepted.

Renal revascularisation

Endovascular treatment is the preferred mechanism of managing medically refractory RAS, although society guidelines detail a limited set of circumstances in which open surgery is indicated.