Renovascular hypertension and ischemic nephropathy

Abstract

Renovascular disease remains among the most prevalent and important causes of secondary hypertension and renal dysfunction. Many lesions reduce perfusion pressure including fibromuscular diseases and renal infarction, but most are caused by atherosclerotic disease. Epidemiologic studies establish a strong association between atherosclerotic renal-artery stenosis (ARAS) and cardiovascular risk. Hypertension develops in patients with renovascular disease from a complex set of pressor signals, including activation of the renin-angiotensin system (RAS), recruitment of oxidative stress pathways, and sympathoadrenergic activation. Although the kidney maintains function over a broad range of autoregulation, sustained reduction in renal perfusion leads to disturbed microvascular function, vascular rarefaction, and ultimately development of interstitial fibrosis. Advances in antihypertensive drug therapy and intensive risk factor management including smoking cessation and statin therapy can provide excellent blood pressure control for many individuals. Despite extensive observational experience with renal revascularization in patients with renovascular hypertension, recent prospective randomized trials fail to establish compelling benefits either with endovascular stents or with surgery when added to effective medical therapy. These trials are limited and exclude many patients most likely to benefit from revascularization. Meaningful recovery of kidney function after revascularization is limited once fibrosis is established. Recent experimental studies indicate that mechanisms allowing repair and regeneration of parenchymal kidney tissue may lead to improved outcomes in the future. Until additional staging tools become available, clinicians will be forced to individualize therapy carefully to optimize the potential benefits regarding both blood pressure and renal function for such patients.

FIGURE 1

(a) MR Angiogram of High grade renal artery stenosis with renal vein renin measurements: lateralization suggests high probability of pressor activity. (b) Renal artery duplex study of distal segments on the right kidney illustrating “parvus tardus” waveform and low resistive index (RI=0.42). These data suggest excellent distal blood flow “runoff' and limited parenchymal fibrosis. Severe hypertension had developed over a three month period that was reversed by successful revascularization. (c) Manifestations of renal arterial disease

FIGURE 1

(a) MR Angiogram of High grade renal artery stenosis with renal vein renin measurements: lateralization suggests high probability of pressor activity. (b) Renal artery duplex study of distal segments on the right kidney illustrating “parvus tardus” waveform and low resistive index (RI=0.42). These data suggest excellent distal blood flow “runoff' and limited parenchymal fibrosis. Severe hypertension had developed over a three month period that was reversed by successful revascularization. (c) Manifestations of renal arterial disease

FIGURE 2

Micro-CT imaging of vascular casts obtained from a swine model of atherosclerotic renal artery stenosis. Atherosclerosis produced by cholesterol feeding induces small vessel proliferation and disturbed endothelial function (middle panel). The kidney beyond a main renal arterial occlusive lesion induced by copper stent experiences dropout (“rarefication”) of small vessels within both cortex and medulla and accelerated tissue fibrosis. From Lerman and Chade, with permission .

FIGURE 3

(a) T2 imaging by MR and CT angiogram demonstrating high grade renal artery stenosis to the left kidney and a normal nephrogram on the right (with a vascular stent in place and distal fibromuscular disease). (b) Parametric maps of R2* (reflecting the level of deoxyhemoglobin) from Blood Oxygen Level Dependent (BOLD) MR at 3 Tesla from the same kidneys are shown below. The right kidney has low cortical R2* (blue) with small areas of medullary deoxygenation typical of a normal kidney. Moderate vascular stenosis such as observed with fibromuscular disease is associated with well-preserved tissue oxygenation as shown here . The small left kidney has higher levels of cortical R2* and a large, deep area of medullary deoxygenation (red) illustrating physiologic oxygen deprivation as a result of extreme vascular compromise. Hence, progressive occlusive disease ultimately overrides compensatory changes within the kidney to produce ischemic injury.

FIGURE 3

(a) T2 imaging by MR and CT angiogram demonstrating high grade renal artery stenosis to the left kidney and a normal nephrogram on the right (with a vascular stent in place and distal fibromuscular disease). (b) Parametric maps of R2* (reflecting the level of deoxyhemoglobin) from Blood Oxygen Level Dependent (BOLD) MR at 3 Tesla from the same kidneys are shown below. The right kidney has low cortical R2* (blue) with small areas of medullary deoxygenation typical of a normal kidney. Moderate vascular stenosis such as observed with fibromuscular disease is associated with well-preserved tissue oxygenation as shown here . The small left kidney has higher levels of cortical R2* and a large, deep area of medullary deoxygenation (red) illustrating physiologic oxygen deprivation as a result of extreme vascular compromise. Hence, progressive occlusive disease ultimately overrides compensatory changes within the kidney to produce ischemic injury.

FIGURE 4

Algorithm for evaluation and intervention in renovascular disease (from Textor, in Brenner's Textbook, with permission