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Renovascular disease (RVD) is a major cause of secondary hypertension. Atherosclerotic renal artery stenosis is the most common type of RVD followed by fibromuscular dysplasia. It has long been recognized as the prototype of angiotensin-dependent hypertension. However, the mechanisms underlying the physiopathology of hypertensive occlusive vascular renal disease are complex and distinction between the different causes of RVD should be made. Recognition of these distinct types of RVD with different degrees of renal occlusive disease is important for management. The greatest challenge is to individualize and implement the best approach for each patient in the setting of widely different comorbidities., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The various types of glomerulonephritis, including many forms of vasculitis, are responsible for about 15% of cases of end-stage renal disease (ESRD). Arterial hypertension represents a frequent finding in patients suffering from glomerulonephritis or vasculitis and hypertension also serves as an indicator for these severe types of diseases. In addition, there are symptoms and signs like hematuria, proteinuria and renal failure. Especially, rapidly progressive glomerulonephritis (RPGN) constitutes a medical emergency and must not be missed by treating physicians. This disease can either occur limited to the kidneys or in the context of a systemic inflammatory disorder, like a vasculitis. If left untreated, RPGN can lead to a necrotizing destruction of glomeruli causing irreversible kidney damage within several months or even weeks. With respect to the immunologically caused vasculitis, there are - depending upon the severity and type of organ involved - many clinical warning signs to be recognized, such as arterial hypertension, hemoptysis, arthalgias, muscle pain, palpable purpura, hematuria, proteinuria and renal failure. In addition, constitutional signs, such as fever and loss of body weight may occur concurrently. Investigations of glomerulonephritis or vasculitis must contain a careful and complete examination of family history and medications used by the respective patient. Thereafter, a thorough clinical examination must follow, including skin, joints and measurement of arterial blood pressure. In addition, a spectrum of laboratory analyses is required in blood, such as full blood screen, erythrocyte sedimentation rate, CRP, creatinine, urea and glucose, and in urine, including urinalysis looking for hematuria, red cell casts and proteinuria. Importantly, proteinuria needs to be quantified by the utilization of a random urine sample. Proteinuria > 3g/d is diagnostic for a glomerular damage. These basic tests are usually followed by more specialized analyses, such as a screening for infections, including search for HIV, hepatitis B or C and various bacteria, and for systemic inflammatory diseases, including tests for antibodies, such as ANA, anti-dsDNA, ANCA, anti-GBM and anti-CCP. In cases of membranous nephropathy, antibodies against phospholipase-A2-receptor need to be looked for. Depending upon the given clinical circumstances and the type of disease, a reasonable tumor screening must be performed, especially in cases of membranous and minimal-change nephropathy. Finally, radiological examinations will complete the initial work-up. In most cases, at least an ultrasound of the kidney is mandatory. Thereafter, in most cases a renal biopsy is required to establish a firm diagnosis to define all treatment options and their chance of success. The elimination of a specific cause for a given glomerulonephritis or vasculitis, such as an infection, a malignancy or a drug-related side-effect, remains the key principle in the management of these diseases. ACE-inhibitors, angiotensin receptor-blockers, aldosteron antagonists and renin-inhibitors remain the mainstay in the therapy of arterial hypertension with proteinuria. Only in cases of persistently high proteinuria, ACE-inhibitors and angiotensin receptor blockers can be prescribed in combination. Certain types of glomerulonephritis and essentially all forms of vasculitis require some form of more specific anti-inflammatory therapy. Respective immunosuppressive drug regimens contain traditionally medications, such as glucocorticoids (e. g. prednisone), cyclosporine A, mycophenolate mofetil, cyclophosphamide, and azathioprine. With respect to more severe forms of glomerulonephritis and vasculitis, the antibody rituximab represents a new and less toxic alternative to cyclophosphamide. Finally, in certain special cases, like Goodpasture's syndrome or severe ANCA-positive vasculitis, a plasma exchange will be useful and even required.

Two critically ill neonates with severe renovascular hypertension as a complication of aortic monitoring catheter are presented. They did not respond to intensive medical therapy for hypertension. In spite of their precarious general condition, nephrectomy was undertaken with complete relief of symptoms.

Percutaneous transluminal angioplasty for renovascular hypertension offers the potential for simple, safe, and relatively inexpensive therapy in certain categories of patients. The technique should be performed only under these conditions: (1) in centers with experience in angiography and angioplasty of peripheral vascular lesions; (2) with an experienced vascular surgical team standing by in case of surgical complications; (3) on lesions anatomically amenable to catheter dilation; and (4) on patients with prior proof of increased renin production on the affected side. Angioplasty is limited by the anatomy of the stenoses. Complications are similar to those of percutaneous angiography and occur with an estimated frequency of 5%-10%. Short-term patency is considered 70%-80%, somewhat lower than the surgical repair result. In all but certain cases where angioplasty offers a relative advantage, randomized controlled studies will be required to determine whether angioplasty or surgery should be the preferred method of therapy.

Seven hypertensive patients underwent percutaneous transluminal angioplasty for relief of arterial stenosis complicating renal allotransplantation. Five had end-to-side anastomosis of the donor renal artery to the recipient external iliac artery, and two had end-to-end anastomosis of the donor renal artery to the recipient internal iliac artery. Each patient had developed hypertension (blood pressure greater than 145/95 mm Hg), elevated peripheral venous plasma renin, and six demonstrated decrease in renal function as detected by an increase in serum creatinine at least 2 months after transplantation and without evidence of rejection. Angioplasty was technically successful without significant complications and blood pressure and biochemical abnormalities were improved or stabilized in all seven patients.

Left ventricular (LV) coronary flow (CF) was determined by left atrial injection of microspheres in conscious rats during the development and after the reversal of LV hypertrophy in 2-kidney, 1-clip Goldblatt hypertension. Two groups of untreated renal hypertensive rats (RHR) were studied, the first (RHR1, n = 17) at 10 weeks and the second (RHR2, n = 9) at 24 weeks after clipping. Beginning 9 weeks after clipping, 2 other groups were treated either with captopril (40 to 60 mg/kg/day) in drinking water (RHR-C, n = 8) or left nephrectomy (RHR-N, n = 9) and followed for 15 weeks. Sham-operated animals followed for similar periods of time served as controls (Sham-1, n = 12, as a control for RHR1, and Sham-2, n = 11, as a control for RHR2). In all groups, LV mass increased or decreased in close correlation with changes in arterial blood pressure, and minimal total LV coronary resistance remained unchanged. The development of hypertrophy was associated with a tendency toward reduction in CF reserve (defined as maximal CF/unit mass); this flow reserve was restored with reversal of hypertrophy. The importance of the relation between pressure and LV mass as a determinant of CF reserve was investigated in a second study in which this relation was changed by altering the periods of captopril therapy; in these cases, CF reserve correlated significantly with the ratio of arterial pressure to LV mass (r = 0.76, n = 12, p less than 0.01). The results suggest that maintenance of CF reserve in LV hypertrophy depends on an appropriate balance between arterial pressure and LV mass, and might be disturbed by antihypertensive therapy that leaves LV hypertrophy unchanged.

Surgical correction of unilateral renal artery stenosis was performed in 31 hypertensive patients. Preoperative renal vein renin ratios (RVRR) before and after dihydralazine stimulation were measured in all patients. Postoperative blood pressure were normal in 12, improved in 17 and unchanged in 2 patients. Six patients did not have renin lateralization, but all were cured or improved after surgery. RVRR was a poor predictor of the results of surgery in patients with unilateral renal artery stenosis.

Collateral circulation and recanalization represent the main problems of organ-ablating renal embolization. Different animal models were used to study the influence of central, peripheral, and capillary occlusion on organ necrosis. The first laboratory experiments were performed to optimize transcatheteral application of the embolization media tested (Gelfoam powder, Histoacryl, Ethibloc). Experiments with the model of a normal rat kidney (n = 400) showed that only capillary embolization homogeneously occluding the entire arterial system resulted in complete organ necrosis, while following central (renal artery ligation) or peripheral (Gelfoam powder) occlusion, areas of intact parenchyma remained. Ethibloc/glucose proved to be the embolization medium best suited for capillary embolization (radiopaque, inert, slow resorption). Studies with the model of unilateral renal hypertension of the rat (n = 146) demonstrated the equivalent therapeutic efficiency on blood pressure of Ethibloc embolization (57% cured, 21% improved) compared to surgical nephrectomy (50% cured, 29% improved), whereas renal artery ligation (85% failed) resulted in minor improvement only. In order to adapt capillary embolization with Ethibloc/glucose to clinical angiographic techniques, we performed angioinfarction of canine kidneys (n = 15): the use of a balloon catheter is mandatory. This guarantees blood stasis during the embolization procedure and avoids embolic reflux. Possible clinical indications of capillary embolization in renal hypertension as a less invasive method are, e.g.: malignant nephrosclerosis; renovascular or glomerulonephritic contracted kidneys, and renal dysplasia. Indications for super-selective vaso-occlusion are renal aneurysms, a-v malformations, and segmental hypoplasia.

We have studied a group of 47 patients with unilateral or bilateral renal artery stenosis; 27 of them have been operated, while 20 have been subjected to medical treatment. Among the surgically treated patients, 18 out of the 22 cases with an unilateral stenosis had satisfactory results and didn't assume any treatment after surgical cure. All the 5 cases of bilateral stenosis presented a regular blood pressure after surgery. Nine among the 12 patients affected by unilateral stenosis and 3 among the 8 patients presenting bilateral forms who received medical treatment had successful results with the conventional therapy. The parameters that seems give a better prognostic indication for the surgical cure are either significant renal veins renin ratios (Ra/Rc and Rc/P), either high peripheral PRA values combined with a renal artery stenosis greater than or equal to 70%, in all the cases without evident damages in the opposite kidney, even if the renin ratios are not significant. The results of the medical treatment may be predicted from the entity of the renal stenosis. Failures are more likely to occur in the bilateral forms. In these cases the most satisfactory results can be obtained using minoxidil or the inhibitor of the converting enzyme of angiotensin I.

1. Removal of the renal artery constriction but not of the clipped kidney restored the blood pressure to normal levels in Goldblatt two-kidney rats with hypertension of more than 4 months' duration. 2. Despite the differences in blood pressure response, both surgical procedures lowered plasma renin concentration to normal or below normal values. 3. Administration of the oral converting enzyme inhibitor SQ 14 225 produced a marked fall in blood pressure in Goldblatt kidney rats with chronic hypertension. However, a prolonged infusion of the angiotensin II antagonist saralasin was quite ineffective. The difference in response to the two inhibitors may have been due to bradykinin potentiation by the converting enzyme inhibitor. 4. Although plasma renin is often elevated in Goldblatt two-kidney rats with hypertension of more than 4 months' duration, the renin-angiotensin system plays no role in the maintenance of blood pressure at this stage.

The authors report an interesting case of dilatation of renal artery stenosis by inflation of the balloon of a catheter engaged in the stenosed arterial lumen inserted percutaneously under arteriographic control. The patient's hypertension responded within a few hours and plasma renin levels in the systemic circulation became normal within a few days. This result was stable at 2 months. In the opinion of the authors, this technique of percutaneous transluminal angioplasty, initially used for arterial obstructions of the lower limbs, carotid and coronary obstructions, should find a wide field of application in the area of renovascular hypertension.

Renovascular hypertension can result from renal artery lesions involving the main renal artery, or its branches. It is generally felt that the elevation of blood pressure results from excessive systemic vasoconstriction secondary to enhanced renin secretion by one or part of one kidney. Renin secretion is enhanced because of constriction of the renal artery and resultant intrarenal ischemia. Clinically patients cannot be distinguished from those with essential hypertension and diagnosis must be made with arteriography although urography and isotope renography may suggest the diagnosis. Surgical cure can be predicted if differential renal vein renin ratios lateralize but a non-lateralizing study does not necessarily mean that surgery will fail. In properly selected patients, surgical results are excellent.

Twenty-six patients with renal vascular hypertension were treated with percutaneous transluminal dilatation. Twenty-one were followed for more than 1 year; 18 underwent repeat angiography. Recurrence of stenosis was shown angiographically in one of six patients with fibromuscular disease and in 12 of 12 patients with atherosclerotic disease. The procedure was more likely to result in cure of hypertension (six of 10) in patients with fibromuscular disease than in patients with atherosclerotic disease (one of 16). Although percutaneous transluminal angioplasty provides the advantages of simplicity, reduced cost, and probably reduced risk, long-term utility of the procedure remains to be established. A prospective randomized trial, establishment of a registry, or both would serve this purpose.

The first reports of surgically curable hypertension in the late 1930s led to enthusiasm among clinicians for removing kidneys with arterial stenosis in hypertensive patients. The development of vascular surgical techniques in the 1950s made it possible to achieve successful renal revascularization in many of these cases. However, the cause and effect relationship between a stenotic renal artery lesion and hypertension was poorly understood and many patients treated surgically had no improvement of blood pressure postoperatively. Continued experience in this field during the past two decades has significantly improved our understanding of the natural history and functional significance of renovascular disorders. Patients with renovascular hypertension can now be identified with a high degree of accuracy and successful renal revascularization is possible in most cases. Nevertheless, multiple factors must be weighed in determining whether medical or surgical therapy is more appropriate for a given patient. These include the causal relationship of renovascular disease to hypertension, the adequacy of blood pressure control with medical therapy, the natural history of untreated renovascular disease with particular regard for the risk of sustaining impaired renal function, the medical condition of the patient, the morbidity and results of surgical therapy, and the availability of other therapeutic options such as percutaneous transluminal dilatation.

The success of digital video subtraction angiography (DVSA) in screening hypertensive patients for renal artery stenosis and the apparent value of percutaneous transluminal angioplasty (PTA) prompted re-evaluation of the philosophy of indiscriminate medical therapy for newly discovered cases of hypertension. DVSA was diagnostic in 87% of cases. The cost of screening for renovascular hypertension by DVSA and treatment by PTA when feasible is about the same as that of medical therapy. Considering the problems of noncompliance and drug side effects associated with medical antihypertensive therapy, DVSA screening for renovascular hypertension in a broader population seems both medically and economically sound.

Malignant hypertension was induced in rats by aortic ligation above the left renal artery. After 7- and 28-day periods of hypertension, the characteristics of the vascular disease were studied and the kidney below the aortic ligation was removed. The blood pressure and the vascular disease were reexamined at the end of the first and fourth weeks after nephrectomy. The evolution of the vascular disease was assessed in the contralateral kidney, in the heart, and in the superior mesentery. The results obtained allowed the following conclusions: 1) when the predominant lesions are of fibrinoid necrosis and moderate intimal hyperplasia without fibromucoid changes (initial phase), the hypertension and the hypertensive vascular disease are completely reversible after the nephrectomy; 2) when the predominant lesions are proliferative endarteritis with fibromucoid changes (chronic phase), neither the hypertension nor the vascular disease are reversible after the left nephrectomy and during the period of follow-up. Therefore, the type of vascular lesion seems to be one important determinant of the reversibility of the hypertensive process after nephrectomy.

Percutaneous transluminal dilatation (PTD; n = 45) was compared with surgical procedures (n = 51) in 96 patients with renovascular hypertension. Since cases with atherosclerotic stenosis (ASS) are known to show a different response to surgery than those with fibromuscular dysplasia (FMD), group-specific analysis was performed. In their two subgroups (ASS and FMD) both surgical and dilated patients showed comparable mean age and sex distribution and serum creatinine. However, differences were observed in mean duration of hypertension and in pretreatment blood pressure values: surgical patients with ASS and FMD showed a lower mean duration of hypertension (operation: ASS 3.2, FMD 1.9 years; PTD: ASS 5.1, FMD 3.4 years) and higher mean blood pressure values (surgery: ASS 207/121, FMD 209/126 mm Hg; PTD: ASS 199/115, FMD 175/108 mm Hg). After a mean observation period of 2.6 years mean blood pressure fell in the surgery group to 147/90 mm Hg in the 26 cases with ASS, and to 139/87 mm Hg in the 25 patients with FMD. In dilated cases respective blood pressure values were 145/90 mm Hg (ASS, n = 17) and 132/84 mm Hg (FMD, n = 11). These results show a comparable blood pressure lowering effect for surgery and dilatation in renovascular hypertension. In cases with lengthy stenosis or involvement of primary branches of the renal artery and in those with aortic or poststenotic renal aneurysm a surgical technique should be performed, whereas in the remaining cases PTD represents a favourable procedure.

The Authors describe the anatomopathological background of different types of renal artery lesion, causing renovascular hypertension. Various pathological aspects of dysplastic lesions are examined and compared with the aspects of arteriosclerotic disease. Finally correlations between angiographic and histological reports are considered, discussing when and how a surgical procedure should be advisable.

Percutaneous transluminal dilatation of a right sided fibrous renal artery stenosis was performed in a 5-year-old boy with severe hypertension. Biochemical and hemodynamic activity of the renal artery stenosis was demonstrated by measurement of renal venous renin concentration and of pre- and poststenotic blood pressure. Hypertension disappeared within 3 weeks and the renin values became normal. The method is less traumatic than operative revascularization and may be an alternative procedure to vascular surgery in the treatment of renovascular hypertension in childhood.

A case of malignant hypertension in a 20-year-old man who self-administered various hallucinogenic drugs is described. Renal angiography showed arteritic changes with aneurysms in renal vessels and focal renal cortical infarction. A dramatic response in terms of resolution of arteritis occurred with prednisone therapy. The impressive use of minoxidil and labetalol in the initial control of the hypertension is also demonstrated.

Diagnosis of renovascular hypertension is of particular interest because it is curable by vascular surgery or percutaneous transluminal angioplasty (PTA). Transvenous digital subtraction angiography (DSA) is a minimally invasive method of importance in detecting renal hypertension of different origins (pre-, intra-, postrenal). This study was carried out to assess the value of transvenous DSA in analyzing the renal arteries and renal parenchyma, in detecting renal artery stenosis, and in controlling PTA results. Our results demonstrate that image quality of transvenous DSA of the renal arteries was excellent (diagnostic in 474 of 510 cases, 93%). A large number (62%) could be analyzed following one injection of contrast medium, in 25% a second, and 6% a third injection was necessary. In follow-up studies after PTA (1 week to 24 months) patients with normalized blood pressure values (16/33) had a completely reopened arterial segment and normal parenchyma of both kidneys. In persistent or recurrent hypertension (17/33) restenosis could be detected by transvenous DSA in 2 cases and renal parenchymal lesions in 8 cases. Reversible intimal dissections observed immediately following PTA had no influence on blood pressure results. Intra-arterial DSA is recommended when renal artery stenosis is to be evaluated for PTA and when the result of balloon catheter dilatation is to be evaluated. Intra-arterial DSA is indicated to exclude stenosis following kidney transplantation and to determine perfusion of the graft (parenchyma and venous return) taking advantage of small volumes and concentrations of contrast material made possible by digital contrast enhancement.

The technique of percutaneous transluminal angioplasty has been shown to be an alternative to vascular surgery in some cases of renovascular hypertension. A 40-year-old woman presented with malignant hypertension on the basis of fibromuscular hyperplasia involving her dominant right renal artery. The stenosis was successfully dilated and her blood pressure returned to normal.

A retrospective study made of 114 cases of renovascular hypertension was undertaken to compare the effectiveness of different types of treatment. In this series, with a follow-up of 18 months to 9 years, a favourable result with regard to blood pressure was obtained in 45% of cases with surgery, in 63% of cases with medical treatment and in 88% of cases if treatment included beta-blockers. Medical treatment represents a valid alternative to surgery in hypertension of this type, regardless of the amount of renin secretion and whatever the criteria of ischaemia. The choice of surgery as a method of treatment thus depends above all upon the age of patient, the type of stenosis and the anatomical risk represented by the vascular malformation. Despite the very spectacular results of medical treatment, it remains essential to seek a renal cause for hypertension, since many renal conditions which require specific treatment present with hypertension alone.

Percutaneous transluminal dilatation of a left-sided renal-artery stenosis was done in a 61-year-old patient with hypertension. Shortly after dilatation blood-pressure fell to normal and renal plasma flow increased. Dilatation might be an alternative to renal vascular surgery in severe renal hypertension.

PTA may be the most cost-effective approach to correctable renovascular hypertension. Successful PTA not only lowers the blood pressure, but may also preserve or improve renal function. Patients who are not ideal surgical risks should be considered for this approach if their blood pressure is not controlled or if side effects from antihypertensive drug therapy are disabling. PTA should be performed in consultation with, and with the back-up of, a vascular surgeon.