Revascularization of Renal Artery Stenosis Versus Medical Therapy for the Treatment of Ischemic Nephropathy (NITER)

• Systolic and diastolic blood pressure values at 0.5, 1 and 2 yrs follow up, with an extended follow up after 2 yrs [ Time Frame: 0.5, 1 and 2 years follow up plus extended 4 yrs ] [ Designated as safety issue: Yes ]
• Number of hypotensive drugs [ Time Frame: 0.5, 1 and 2 years follow up plus extended 4 yrs ] [ Designated as safety issue: Yes ]
• Results of renal scintigraphy [ Time Frame: 0.5, 1 and 2 years follow up plus extended 4 yrs ] [ Designated as safety issue: Yes ]
• Incidence of complications due to interventional manoeuvres [ Time Frame: 0.5, 1 and 2 years follow up plus extended 4 yrs ] [ Designated as safety issue: Yes ]
• Changes in the incidence of vascular complications in extra-renal districts [ Time Frame: 0.5, 1 and 2 years follow up plus extended 4 yrs ] [ Designated as safety issue: Yes ]

The aim of the study is to value, in patients with chronic kidney disease and hypertension, whether medical therapy plus interventional renal artery revascularization is superior to medical therapy alone for the treatment of hemodynamically significant (>70%) atherosclerotic renal artery stenosis, diagnosed by duplex doppler ultrasonography and confirmed by magnetic resonance angiography, in terms of avoidance of the progression of renal damage, control of hypertension and in reducing the cerebro and cardiovascular complications.

Atherosclerotic renovascular disease (ARVD), due to renal hypoperfusion caused by mono or bilateral renal artery stenosis (RAS), is a increasing cause of chronic kidney disease and many elderly patients start dialysis due to ARDVD. Moreover ARVD is frequently progressive and reduces life-expectancy more than other causes of end stage renal disease, with a mortality rate higher than in patients with stable angina, similar to that of patients operated for colon cancer.

Unfortunately, there is not a definite therapy to cure this disease, despite important advancements in both medical therapy and in interventional radiology. Aim of the study is to see whether percutaneous transluminal interventional radiology plus stenting (PTRS) of the renal artery offers more, in terms of both preventing the progression of renal failure and controlling the hypertension, compared with the medical therapy addressed to control hypertension, improve the dyslipidemic profile and optimise the platelet anti-aggregant therapy, following the most recent guidelines. The eligible patients will be centrally randomized to:

1. medical treatment with hypotensive drugs (all class of hypotensive agents will be used according to single-center experience including drugs agent on renin-angiotensin-aldosterone-system, when permitted), lipid lowering therapy (namely all class of statins-or hydroxymethylglutaryl-coA reductase inhibitors)and anti-platelet (acetylsalicylate and/or ticlopidine or clopidrogel according to single-center experience) or to
2. the same medical therapy, as previously described in group a, associated with PTRS, according to a standardized protocol, with a follow up at 2 years extended to other 2 years

• Atherosclerosis
• Chronic Kidney Disease
• Hypertension, Renovascular
• Ischemic Nephropathy
• Renal Artery Stenosis

• Drug: Medical treatment
  hypotensive drugs, statins and anti-platelets
• Procedure: PTRS
  Percutaneous transluminal renal artery stenting. The same medical therapy, as in group A, plus PTRS
• Device: renal artery stent
  Non-drug intervention, percutaneous transluminal renal artery stent angioplasty
• Device: renal artery stent
  Adding the renal artery stenting (in group B) to the optimal medical therapy (as in group A) that includes hypotensive drugs, statins and antiplatelet therapy

• Experimental: B:PTRS
  B: the same medical therapy, as previously described in group A, associated with PTRS
  Interventions:

  • Procedure: PTRS
  • Device: renal artery stent
  • Device: renal artery stent
• Active Comparator: A:medical therapy
  hypotensive drugs, statins and antiplatelet therapy
  Interventions:

  • Drug: Medical treatment
  • Device: renal artery stent

Inclusion Criteria:

• Age ≤ 80 years
• Presence of ostial renal artery stenosis ≥ 70% (determined by Duplex Doppler ultrasonography and confirmed by Magnetic Resonance valuated by at least two experienced operators)
• Serum creatinine ≤ 3 mg/dl and/or creatinine clearance (Modification of Diet in Renal Disease, MDRD formula)≥ 30 ml/min, defined as stage 3 or greater CKD based on National Kidney Foundation classification
• Longitudinal ultrasonographic diameter of the stenotic kidney ≥ 8 cm
• Blood pressure values ≤ 150/90 mmHg with the use of less than four hypotensives drugs

Exclusion Criteria:

• Age > 80 years
• Other well-known nephropathy cause of renal failure
• Duplex doppler ultrasonography Resistive Index values >0.8
• Total occlusion of renal artery lumen
• Occurrence of cerebral or cardiac vascular diseases in the 6 months before the enrolment in the study
• Malignancy with a life expectation less than one year
• Previous documented cholesterol thrombo embolization episodes (clinically, bioptically or instrumentally)
• Liver failure
• Cardiac failure (NYHA IV class) or instable angina
• Well-known intolerance or contraindications to the use of iodinated contrast media, to statins or to anti platelets drugs
• Previous renal angioplasty
• Pregnancy